1. [Cytotoxic effects of the novel photosensitizer PEG-MTPABZ-PyC-mediated photodynamic therapy on gastric cancer cells].
作者: Lingjuan Chen.;Qi Wang.;Lu Wang.;Yifei Shen.;Haibin Wang.;Hengxin Wang.;Xuejie Su.;Meixu Lei.;Xianxia Chen.;Chengjin Ai.;Yifan Li.;Yali Zhou.
来源: Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2025年50卷7期1137-1144页
The application of photodynamic therapy in solid tumors has attracted increasing attention in recent years, and the efficiency of photosensitizers is a crucial determinant of therapeutic efficacy. This study aims to evaluate the cytotoxic effects of a novel photosensitizer, PEG-MTPABZ-PyC, in photodynamic therapy against gastric cancer cells.
2. [Neurocutaneous melanosis in children caused by NRAS gene variation: a clinicopathological and molecular genetic analysis of three cases].
Objective: To investigate the clinicopathological and molecular characteristics of neurocutaneous melanosis in children caused by NRAS gene variants. Methods: Three cases of neurocutaneous melanosis from Children's Hospital of Fudan University (case 1 and case 2) and Shanghai Children's Hospital, School of Medicine Shanghai Jiaotong University (case 3) from July 2022 to February 2023 were collected. The clinical, histopathological, immunohistochemical and genetic results of three patients were retrospectively analyzed. The literatures were reviewed. Results: The patients were all female, aged 5, 4 and 3 years, respectively. The patients presented with severe headache with other symptoms of increased intracranial pressure. Physical examination showed multiple congenital melanocytic nevi throughout the body. Imaging examination showed intracranial masses, which were located in the right cerebellum, pineal gland and left temporal lobe, respectively. The maximum diameters were 39.1 mm, 72.8 mm and 52.2 mm, respectively. Histologically, the tumor showed diffuse sheets of round or oval-shaped cells arranged in nests, with marked nuclear atypia, eosinophilic cytoplasm, dark nuclei, and prominent nucleoli. Giant tumor cells were seen and mitotic figures were easily observed. There were hemorrhage and necrosis. Pigment granules were found in the cytoplasm and stroma in case 1 and case 2. Immunohistochemically, the tumor cells showed diffuse and strong staining of SOX10, S-100, HMB45 and Melan A, but did not express GFAP and CKpan. The Ki-67 proliferation index ranged from 30% to 80%. Genetic testing showed that case 1 and case 2 had NRAS Q61K matation, and case 3 had NRAS Q61R mutation. Case 1 and case 3 underwent complete resection of the tumor combined with chemotherapy. Case 2 was diagnosed by biopsy and underwent resection after chemotherapy and radiotherapy. All patients were followed up for 18, 21 and 25 months, respectively. All patients died due to complications such as increased intracranial pressure and hydrocephalus. Conclusions: Neurocutaneous melanosis is a congenital neurocutaneous syndrome caused by abnormal development of embryonic neuroectodermal melanoblasts. Most cases are associated with somatic mutations of NRAS gene. Clinicians should pay attention to the skin manifestations and neuroimaging examination in patients with unexplained intracranial hypertension or epilepsy. The diagnosis of neurocutaneous melanosis depends on histopathology and genetic testing.
3. [Association between HER2 overexpression and recurrence rate in patients with non-muscle-invasive bladder cancer following anthracycline-based intravesical instillation therapy].
作者: K M Li.;M L Liu.;S F Wu.;R P Hong.;Y Y Liu.;L L Zeng.;Z Y Liang.;X Zeng.
来源: Zhonghua Bing Li Xue Za Zhi. 2025年54卷11期1193-1198页
Objective: To assess the clinicopathological characteristics of non-muscle-invasive bladder cancers (NMIBC) with high expression of human epidermal growth factor receptor 2 (HER2) and to examine the prognostic values of HER2 expression in NMIBC patients with intravesical anthracycline instillation. Methods: A total of 221 NMIBC samples diagnosed between January 1, 2017 and April 15, 2024 were collected. Their clinical, diagnostic and treatment features were analyzed. The expression of HER2 protein and the Ki-67 proliferation index were assessed using immunohistochemistry (IHC). For the patients with HER2 high-expression (IHC 3+), the clinical pathological features (age, gender, tumor grade, Ki-67 expression level, tumor size, and tumor number) were compared with those without (i.e., HER2 IHC 0/1+/2+). The impact of HER2 expression on the recurrence-free survival (RFS) of patients with intravesical anthracycline (epirubicin or pirarubicin) instillation after transurethral resection of bladder tumor (TURBT) was evaluated. Results: Among the 221 NMIBC patients, 30 (13.6%) were HER2 IHC 3+, 142 (64.3%) HER 2+, 46 (20.8%) HER2 1+, and 3 (1.4%) HER2 IHC 0. The proportion of high-grade tumors in patients with HER2 high-expression was higher than that in patients without (83.3% versus 44.5%, P<0.001). Additionally, a high Ki-67 index (≥20%) was more commonly noted in HER2 high-expression tumors (P=0.003). In the patients treated with intravesical anthracycline instillation, HER2 high-expression was associated with a shorter RFS (P<0.001). Conclusion: HER2 high-expression seems to be not only associated with worse clinicopathological features of NMIBC but also a poor RFS in NMIBC patients treated with anthracycline instillation after TURBT.
4. [CD117-positive eosinophilic renal cell tumors with uncertain classification: a clinicopathological and molecular genetic analysis of 10 cases].
作者: B Xie.;Y Huang.;Z L Hu.;J M Feng.;K Tong.
来源: Zhonghua Bing Li Xue Za Zhi. 2025年54卷11期1186-1192页
Objective: To investigate clinicopathological and molecular genetic characteristics of CD117-positive eosinophilic renal cell tumors (ERCTs) with unusual morphological and immunophenotypic features. Methods: Formalin-fixed, paraffin-embedded tissues from 10 cases (9 cases from Xiangya Hospital, Central South University and 1 case from Bishan Hospital of Chongqing Medical University) of diagnostically challenging CD117-positive ERCTs between January 2017 and October 2024 were collected. Histological reviews were performed on HE-stained sections, followed by immunostaining and whole-exome sequencing (WES). Results: The 10 patients were composed of 4 males and 6 females, with ages ranging from 29 to 57 years, median 49.5 (36.8, 51.8) years. The sizes of tumors ranged from 2.5 to 6.0 cm, median 4.8(2.9,5.2) cm. All 10 ERCTs were composed of variably eosinophilic cells and characterized by prominent morphological features including exclusively eosinophilic (2 cases), focal chromophobe-like (3 cases), prominent nested (2 cases), prominent flocculent cytoplasm (1 case), a collision of renal oncocytoma (RO)/chromophobe renal cell carcinoma (ChRCC) (1 case), and diffusely degenerative atypia (1 case). Immunohistochemically, a subset of 10 tumors variably expressed CK7 (7/10) and vimentin (3/10), while they were all positive for CD117 (10/10), PAX8 (10/10), SDHB (10/10), and FH (10/10) and negative for CAⅨ (10/10) and 2SC (10/10). The Ki-67 proliferation index ranged from 1% to 5%. WES identified a GNAS mutation in one case of the RO/ChRCC collision tumor, while no characteristic mutations of other renal cell tumor types were detected in the remaining 9 cases. The analysis of copy number variations revealed complex karyotypic alterations in 4 tumors, harboring various gain of chromosomes 4, 5, 7, 12, 13, 15, 16, 18, and 22, with 3 cases showing variable loss of chromosomes 1, 2, 6, 10, 13, and 17. These 4 cases were molecularly classified as eosinophilic ChRCC. The remaining 6 cases, including 2 cases with a normal diploid karyotype and 4 cases with slight karyotypic alterations, were molecularly classified as 5 ROs and 1 RO-dominant RO/ChRCC collision tumor. Finally, the original diagnosis was retained in 4 cases and revised in 6 cases. Conclusions: CD117-positive ERCTs with uncertain classification may exhibit various morphological overlaps, non-classic histological features, and aberrant immunophenotypes. Combined immunostaining of CK7, CD117, vimentin, SDHB, FH, and 2SC can greatly help discriminate among these tumors and their mimics. When the diagnosis is challenging based only on morphology and immunohistochemistry, molecular genetic tests may be useful.
5. [Pathological characteristics of cytologically diagnosed metastatic clear cell renal cell carcinomas].
作者: W J Cui.;P Z Hu.;Y M Wang.;J Y Liu.;Z Wang.;X Fu.
来源: Zhonghua Bing Li Xue Za Zhi. 2025年54卷11期1180-1185页
Objective: To investigate the clinical, cytopathological characteristics, and differential diagnosis of metastatic clear cell renal cell carcinomas (CCRCC). Methods: Nine cases of metastatic CCRCC cytologically diagnosed in the Department of Pathology, the First Affiliated Hospital of Air Force Medical University from July 2021 to December 2024 were collected. The HE staining, May-Grunewald-Giemsa staining, liquid-based slides, cell block preparation, and immunocytochemistry of EnVision two-step staining were performed. The clinical and cytopathological features, treatments and follow-up data were analyzed in combination with literature review. Results: Among the 9 cases of metastatic CCRCC, there were 7 males and 2 females. The age range was 43-78 years, and the average age was 63.6 (57.5, 72.5) years. The metastatic sites were lymph node in 3 cases (2 cases of mediastinal lymph nodes and 1 case of left cervical lymph node), bone in 3 cases (pubis, thoracic vertebrae and femur, respectively), thyroid in 2 cases, and adrenal gland, lung and pancreas in 1 case, respectively. Two of the 9 cases had two metastatic sites (case 8 had metastases of lung and mediastinal lymph nodes; case 9 had metastases of thyroid and cervical lymph nodes). The median time from the diagnosis to metastasis was 9.4 years (range 1.1 to 13.8 years). The tumor cells were arranged in papillary, acinar, sheet, cluster or single scattered pattern. Most cases had uniform nuclei with mild atypia and inconspicuous nucleoli, while some cases had variable nuclei with prominent nucleoli. The cytoplasm of the tumor cells was abundant. Some cases showed clear cytoplasm with small vacuoles, while some of them showed eosinophilic and granular cytoplasm. Immunocytochemically, the tumor cells were positive for CKpan(AE1/AE3,6/6), PAX8 (9/9), CAⅨ (9/9), CD10 (9/9), and vimiten (8/8). Patients were treated primarily with targeted therapy and/or immunotherapy and curettage and radiation therapy for bone lesions. The follow-up time ranged from 1.0 month to 41.5 months (median, 20 months), and all patients survived at the end of follow-up. Conclusions: The cytology of metastatic CCRCC often shows uniform cell size, abundant and clear cytoplasm, low nuclear/cytoplasmic ratio, and mild nuclear atypia. Its cytological diagnosis is challenging because it occurs in various sites and needs to be differentiated from primary tumors of these sites. Emphasis should be placed on the morphological recognition of CCRCC, and immunocytochemical staining should be used to improve diagnosis. When necessary, molecular testing can be employed for diagnosis. Meanwhile, the medical history should be carefully inquired by pathologists to avoid missed diagnosis and misdiagnosis.
6. [Pulmonary hamartoma: a clinicopathological analysis of 316 cases].
作者: Y Dong.;F Q Meng.;H D Hu.;L H Shen.;Q Q Zhang.;X Y Jin.;J Zou.
来源: Zhonghua Bing Li Xue Za Zhi. 2025年54卷11期1172-1179页
Objective: To investigate the clinicopathological features, pathological classification, and molecular characteristics of pulmonary hamartomas. Methods: A retrospective analysis was conducted on 316 cases of pulmonary hamartomas diagnosed at Nanjing Chest Hospital, Nanjing, China from January 2015 to June 2024. Next generation sequencing (NGS) was performed on 15 cases of this study. The clinical data, histopathological features, immunophenotypes, and molecular alterations were analyzed. Relevant literature was reviewed. Results: Among the 316 patients, there were 154 males and 162 females, with an average age of 56±10 years. Among the 316 cases, 310 were intrapulmonary hamartomas and 6 were intraluminal bronchial hamartomas. Microscopically, there were complex proliferative mesenchymal components and epithelial components, presenting various combinations and hamartomatous morphologies. These hamartomas were morphologically classified into mesenchymal-type hamartomas (cartilaginous, fibrous, smooth muscle, adipose tissue, and mixed types) and epithelial-mesenchymal mixed-type hamartomas (respiratory epithelial-mesenchymal mixed and mucosal gland-mesenchymal mixed types). The cartilaginous hamartomas accounted for 72.8% (230/316) of them, and the non-cartilaginous hamartoma accounted for 27.2% (86/316). Secondary changes such as calcification, ossification, collagenization, mucin degeneration, and cystic changes were commonly present. The immunophenotype was CK7+/TTF1+ for respiratory epithelial cells, or TTF1-/CK7+/p40+ for interstitial cells. Interstitial cells might express desmin, SMA, S-100, caldesmon, etc, while CD34+/CD10+/ER+ spindle-shaped interstitial cells were also commonly noted. Genetic variations were detected in 11 of the 15 cases that were subject to NGS, including HMGA2-related fusion genes, EP300 mutations, FLT1 mutations, JAK1 mutations, SETD2 and TAP2 mutations, and high-copy amplification of CDK4/PHF1/TSPAN31. The patients were followed up for 6 to 110 months without any known recurrence or metastasis. Conclusions: Pulmonary hamartomas mainly occur in the peripheral lung parenchyma, with the cartilaginous type being the most common. Their clinical pathological and molecular features of pulmonary hamartomas are characterized and the histological types are roughly ascertained in this study, with emphasis of the key points of diagnosis and differential diagnosis. Classification of pulmonary hamartomas is valuable for guiding future research. Pulmonary hamartomas overall have a good prognosis. However, those with cystic changes or intraluminal hamartomas in the bronchus may cause serious airway lesions and therefore require special attention.
7. [Clinicopathological and molecular genetic heterogeneity of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young].
作者: X L Su.;J W Wu.;P L Wang.;L W Hu.;Y P Chen.;C H Ren.;F L Song.;H R Lin.;S Zhang.;X F Wang.
来源: Zhonghua Bing Li Xue Za Zhi. 2025年54卷11期1163-1171页
Objective: To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values. Methods: A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed. Results: Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis. Conclusions: Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.
8. [Clinicopathological characteristics and genetic alterations of undifferentiated embryonal sarcoma of the liver in children].
作者: J Y Zheng.;C Zhao.;J Liang.;Y H Pan.;W Hu.;L Y Tang.;C K Shao.;J N Chen.
来源: Zhonghua Bing Li Xue Za Zhi. 2025年54卷11期1156-1162页
Objective: To investigate the clinicopathological characteristics and genetic alterations of undifferentiated embryonal sarcoma of the liver (UESL). Methods: Three cases of UESL diagnosed in the Department of Pathology, the Third Affiliated Hospital of Sun Yat-sen University from 2020 to 2023 were retrospectively collected. The clinical, histomorphological, immunohistochemical, and genetic profiles were reviewed and analyzed. Results: The cohort comprised of three patients, including one male and two females, aged 7, 9, and 15 years, respectively. Tumor locations were in the right lobe of the liver in two cases, and in both the right and left lobes in one case. One case exhibited tumor rupture with hemorrhage. Gross examination revealed solid tumors in gray-red fleshy appearance, with areas of hemorrhage and necrosis. Microscopically, the tumor was composed of irregularly shaped spindle and polygonal cells arranged in bundles or sheets with varying density, scattered within a myxoid matrix containing giant tumor cells and eosinophilic globules. The tumor cells were positive for Vimentin, CD56, CD68, and bcl-2, with a Ki-67 index of 30%-80%. INI1 expression was retained, while p53 exhibited a mutant pattern. CKpan, CK7, CK19, EMA, HepPar-1, Arginase-1, AFP, CD34, S-100, Myogenin, and MyoD1 were negative. All three cases harbored TP53 missense mutations. Case 1 also showed MDM2 copy number amplification (class Ⅰ mutation), and case 2 exhibited a frameshift mutation in exon 10 of TSC2 (class Ⅱ mutation). Additionally, several class Ⅲ mutations were identified in all three cases. Germline testing for tumor-related genetic variants in case 2 revealed a missense mutation in exon 12 of DICER1, an in-frame insertion mutation in exon 8 of MSH2, and a missense mutation in exon 30 of TSC2. Conclusion: UESL is a rare malignant mesenchymal tumor of the liver, predominantly affecting children, with distinctive clinicopathological features and genetic alterations. TP53 mutations may play a key role in the pathogenesis of this tumor.
9. [Consistency of claudin 18.2 expression with antibodies of different clones in gastric adenocarcinoma].
作者: C S Wang.;D Zhang.;X Zhang.;F C Liu.;Q Y Shi.;H Y Wu.;H P Xia.;Q Sun.;L Li.
来源: Zhonghua Bing Li Xue Za Zhi. 2025年54卷11期1144-1149页
Objective: To explore the consistency of claudin 18.2 immunohistochemistry (IHC) using 4 different clone antibodies in gastric adenocarcinoma. Methods: A total of 226 gastric adenocarcinomas diagnosed and treated at the Drum Tower Hospital Affiliated to Nanjing University Medical College between January 2022 to March 2023 were included in this study. The cohort consisted of 165 males and 61 females, with a mean age of (61.3±12.1) years. Tumor tissues from radical resection specimens were collected for tissue microarrays. IHC detection of claudin 18.2 was performed using the EnVision method, utilizing 4 clones of antibody: OTIR157B5, 43-14A, EPR19202 and D313D22. The results were interpreted based on both the intensity of staining on tumor cell membranes and the percentage of positive tumor cells relative to the total tumor cells. Results: The positive cutoff value was set as moderately to strongly linear membrane staining in ≥75% of all viable invasive tumor cells, and clone OTIR157B5 demonstrated the highest positive expression rate at 52.2% (118/226). Additionally, the clones OTIR157B5, 43-14A, and EPR19202 were consistently and strongly positive, with all agreement rates of Cohen κ exceeding 0.8. In gastric adenocarcinoma and its three Lauren subtypes, OTIR157B5 exhibited clear membranous localization. Conclusions: Clone OTIR157B5 of claudin 18.2 antibody shows the highest rate of moderately to strongly linear membrane-positive staining, accounting for ≥75% of all viable invasive tumor cells, and clones 43-14A and EPR19202 show strong consistency and high sensitivity.
10. [Advances in the pathology of breast in China over the past ten years: retrospect and prospect].
In the past decade, breast pathology in China has made significant progress in diagnostic standards, technological applications, scientific research, and discipline development. The histopathological diagnostic system has been continuously refined, with the implementation of relevant guidelines and expert consensus enhancing standardization and reproducibility of diagnostic results. Immunohistochemistry and molecular testing technologies have become increasingly sophisticated, with emerging biomarkers such as low HER2 expression and PIK3CA mutations gradually integrated into clinical decision-making, promoting the advancement of precision therapy. The application of digital pathology and image-assisted analysis has steadily expanded, providing new tools to improve diagnostic efficiency and consistency. The national breast pathology group has actively advanced the development of tiered diagnostic systems, workforce training, and public education, effectively strengthening diagnostic capabilities at the grassroots level. Looking ahead, the integration of multidimensional data, optimization of auxiliary diagnostic systems, and interdisciplinary collaboration are expected to drive the continued development of breast pathology in China.
11. [Opportunities and challenges in the pathological diagnosis of pediatric tumors in the molecular and artificial intelligence era].
Pediatric tumors differ significantly from adult cancers, possessing unique developmental origins, histological features, and molecular genetic changes. With the rapid advancement of multi-omics technologies, such as genomics, transcriptomics, proteomics, and epigenetic analyses, the molecular characteristics of pediatric tumors have been extensively revealed, providing new possibilities for precision medicine. Concurrently, the integration of artificial intelligence and digital pathology has effectively enhanced diagnostic accuracy, presenting a broad scope for future development. While this progress positively impacts the pathological diagnosis of pediatric tumors, it also presents challenges related to data complexity, technology integration, and the promotion of clinical applications. This article aims to discuss the influence of molecular and artificial intelligence, as well as multimodal integrated pathological models on diagnosis and prognostic prediction of pediatric tumor, with the goal of fostering further exploration and in-depth research.
12. [Correct understanding of pathological evaluation and prognostic value of the invasion depth of early colorectal cancer (pT1)].
Colorectal cancer (CRC) is one of the most malignant tumors with high morbidity and mortality worldwide. Early diagnosis and accurate pathological evaluation are of great significance for improving patient prognosis. Endoscopic resection is the main treatment for early CRC. Pathological parameters-such as margin status, lymphatic vascular invasion (LVI), tumor grade, depth of submucosal invasion and tumor budding are the key to determine whether curative resection is achieved. At present, the measurement method of submucosal invasion depth of pT1 CRC is controversial. Submucosal invasion depth measurement adopts different measurement methods for pedunculated and sessile lesions, mainly including measurement from the surface of the lesion or the lower edge of the mucosal muscle layer. Especially for sessile lesions, due to different observers different understandings of the position of the mucosal muscle layer that can be identified or evaluated in the guidelines, observers may apply different criteria to evaluate the integrity of the mucosal muscle layer. In recent years, more and more evidence has shown that the association between the depth of submucosal invasion and the risk of lymph node metastasis may be overestimated, while other pathological parameters (such as LVI, high-grade tumor budding, and poorly differentiated components) have equal or more important significance in prognostic stratification. Therefore, the current measurement of the depth of submucosal invasion of pT1 CRC and its prognostic value are facing challenges, which deserve our attention and further exploration.
13. [Potential value of HPV integration testing in a triage management for HPV-positive women].
作者: J J Li.;W Y Guan.;C Z Chu.;Y Y Chen.;S Y Liu.;G H Peng.;Y Zhang.;Q Weng.;Y Hong.;Y Gu.
来源: Zhonghua Fu Chan Ke Za Zhi. 2025年60卷10期788-797页
Objective: To investigate the dynamic characteristics of human papillomavirus (HPV) genomic integration during cervical lesion progression and the clinical value of HPV integration detection in stratify HPV-positive women, and to explore its molecular mechanisms in cervical carcinogenesis. Methods: A prospective cohort study was designed to enroll high-risk HPV (HR-HPV) positive women who underwent cervical cancer screening in Drum Tower Hospital Affiliated to Nanjing University Medical School and Nanjing Maternity and Child Health Care Hospital from July 2022 to July 2024. Cervical exfoliated cells samples were collected, and HPV whole genome targeted capture and high-throughput sequencing technology were used. The HPV integration patterns, host gene functional region distribution and pathway enrichment characteristics of 157 samples with different cervical lesions grades were analyzed, including 31 cases of normal cervix, 40 cases of cervical intraepithelial neoplasia (CIN) Ⅰ, 32 cases of CIN Ⅱ, 42 cases of CIN Ⅲ, and 12 cases of cervical cancer. Results: HR-HPV integration was detected in 80.2% (126/157) of the 157 HR-HPV positive samples. The incidence of HR-HPV integration in cervical cancer patients was 12/12, which was higher than that in normal women (77%, 24/31). The incidence of HPV16 integration was significantly higher in high-grade lesions, and the incidence of HPV16 integration was 43% (18/42) in CIN Ⅲ patients and 8/12 in cervical cancer patients (P<0.001). A total of 14 438 integration events were detected in 126 samples with HPV integration. The integration sites were mainly distributed in the host intergenic region (51.0%, 7 359/14 438) and intronic region (38.1%, 5 494/14 438), and the integration frequency of viral L1 gene was the highest (28.4%, 4 498/16 781). Functional enrichment analysis showed that HPV integration-related host genes were significantly enriched in transport of small molecules,cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway, and purine ribonucleotide biosynthetic process, which synergistically drove carcinogenesis through multiple mechanisms. Conclusions: HPV integration events are significantly associated with the progression of cervical lesions. HPV integrated detection based on cervical exfoliated cells is expected to optimize the current screening strategy, reduce excessive intervention of HPV positive women and facilitate their accurate triage management.
14. [Identification of paraglottic space invasion in enhanced CT scans of hypopharyngeal cancer by 3D super-resolution reconstruction technology and deep learning].
作者: W L Wang.;Z W Liu.;J A Li.;C Y Xu.;D M Wei.;Y Qian.;W M Li.;D P Lei.
来源: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2025年60卷10期1232-1242页
Objective: To develop a deep learning model based on 3D super-resolution reconstruction technology and to analyze its feasibility and effectiveness in predicting paraglottic space invasion in hypopharyngeal cancer. Methods: A retrospective study was conducted involving 382 patients with hypopharyngeal squamous cell carcinoma treated at Qilu Hospital of Shandong University between January 2014 and December 2020. The cohort included 364 males and 18 females, with a mean age of 62±7 years. Patients were divided into a training set (n=300) and a test set (n=82) based on enrollment time. A generative adversarial network was used to perform 3D super-resolution reconstruction on contrast-enhanced CT images, improving spatial resolution by 16 times. A 2.5D deep learning strategy was employed to construct Resnet-NR and Resnet-SR models based on conventional and super-resolution images, respectively, to predict whether the paraglottic space was invaded. Model performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). A multi-reader multi-case study was conducted to assess the impact of the artificial intelligence (AI) model on clinicians' diagnostic capabilities. Results: The super-resolution model Resnet-SR achieved the highest accuracy in both the training set (AUC=0.87, 95%CI: 0.84-0.90) and the test set (AUC=0.88, 95%CI: 0.81-0.96), significantly outperforming traditional clinical indicators (T stage, N stage, tumor diameter, and pathological differentiation degree) (AUC range: 0.55-0.70, all P<0.05). In comparison, the conventional-resolution model Resnet-NR achieved AUCs of 0.81 (95%CI: 0.77-0.84, P=0.005) and 0.80 (95%CI: 0.71-0.89, P=0.184) in the training and test sets, respectively. Using Resnet-SR to assist clinical decision-making improved the diagnostic accuracy of junior physicians (AUC=0.793 without AI assistance vs. AUC=0.871 with AI assistance, P=0.012) and significantly reduced diagnosis time for clinicians of all experience levels (86.5 s without AI assistance vs. 82.5 s with AI assistance, t=2.01, P=0.032). Conclusion: This study successfully develops a deep learning model based on 3D super-resolution reconstruction technology, which can assist in preoperative prediction of paraglottic space invasion in hypopharyngeal cancer. The AI-assisted tool improves diagnostic accuracy for junior physicians and enhances diagnostic efficiency for clinicians across all experience levels.
15. [Impact of induction chemotherapy sensitivity on prognosis in locally advanced hypopharyngeal cancer: a single-center retrospective cohort study].
作者: Y J Shen.;T Wang.;H L Gong.;C D He.;H Ding.;C W Zhai.;M Zhang.;L Tao.;L Zhou.
来源: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2025年60卷10期1215-1222页
Objective: To assess the impact of induction chemotherapy sensitivity on the prognosis and larynx preservation rates in patients with locally advanced hypopharyngeal cancer and to identify risk factors influencing induction chemotherapy sensitivity. Methods: This study included patients with locally advanced (stage III-IV) hypopharyngeal cancer who received induction chemotherapy as initial treatment at the Eye & ENT Hospital of Fudan University between August 2017 and September 2022. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, enrolled patients were classified into the sensitive group and the resistant group according to their response to induction chemotherapy. Chi-square tests and Log-rank tests were used to compare the objective response rate (ORR), overall survival (OS), progression-free survival (PFS), and laryngeal preservation rate (LPR) between groups. Propensity score matching (PSM) was employed to accurately evaluate the impact of induction chemotherapy sensitivity on prognosis in real-world settings. Univariate and multivariate logistic regression analyses were performed to identify risk factors for induction chemotherapy resistance in locally advanced hypopharyngeal cancer. Results: A total of 197 patients with locally advanced hypopharyngeal cancer who received induction chemotherapy as initial treatment were included in, comprising 195 males and 2 females, with ages ranging from 36 to 74 years. Among them, 155 patients (78.68%) were classified into the sensitive group and 42 patients (21.32%) into the resistant group. The overall response rate (ORR) of induction chemotherapy in this cohort was 78.68%, with a five-year OS rate of 63.7%. The sensitive group had significantly better OS (mOS 6.32 vs. 5.05 year), PFS (mPFS 5.71 vs. 3.09 year) and a significantly higher LPR (91.6% vs. 69.0%) (P<0.05). After propensity score matching, all covariates were balanced between the two groups, and the sensitive group showed significant improvement in OS (P<0.05), while, no significant difference was observed in PFS and LPR between the two groups. Logistic regression analysis revealed that risk factors for induction chemotherapy failure in locally advanced hypopharyngeal cancer included: smoking status (OR [95%CI]=4.751 [1.887-11.961]), tumor location in the posterior pharyngeal wall (OR [95%CI]=2.988 [1.264-7.063]), and cN2-3 stage (OR [95%CI]=3.641 [1.109-11.954]) (P<0.05). Conclusions: Induction chemotherapy sensitivity significantly affects the prognosis of locally advanced hypopharyngeal cancer, which is influenced by various risk factors, including smoking status, tumor sublocation, and clinical N stage.
16. [Expression and prognostic value of mothers against decapentaplegic homolog 7 in head and neck squamous cell carcinoma].
作者: Haihui Zhao.;Xiaojuan Zhong.;Yi Huang.;Wei Fei.
来源: Hua Xi Kou Qiang Yi Xue Za Zhi. 2025年43卷5期660-670页
This study aimed to explore the biological functions and clinical value of mothers against decapentaplegic homolog (SMAD) 7 in head and neck squamous cell carcinoma (HNSCC) through bioinformatics analysis and basic experiments.
17. [A Case of Metastatic Non-small Cell Lung Cancer with Rare BRAF p.L485_T488delinsF Mutation Treated with Dabrafenib and Trametinib].
作者: Yunfei Wang.;Wen Zhao.;Chuang Yang.;Rongyu Zhang.;Chengjun Wang.;Chunyan Han.;Jisheng Li.
来源: Zhongguo Fei Ai Za Zhi. 2025年28卷8期638-643页
The v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene is one of the most critical proto-oncogenes and functions as a key regulator in the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway. The incidence of BRAF mutations in non-small cell lung cancer (NSCLC) patients ranges from 1.5% to 5.5%, with BRAF V600 mutations accounting for approximately 30%-50% of all BRAF mutations, among which BRAF V600E represents the most prevalent mutation type. Currently, the combination of Dabrafenib and Trametinib has been recommended as first-line therapy for BRAF V600-mutant NSCLC by multiple domestic and international guidelines including National Comprehensive Cancer Network (NCCN), European Society of Medical Oncology (ESMO), and Chinese Society of Clinical Oncology (CSCO). However, there are no clear targeted treatment recommendations for BRAF non-V600 mutations. Although case reports suggest that Dabrafenib combined with Trametinib may be effective for patients with BRAF non-V600 mutations, the efficacy and safety require further validation due to limited sample size and lack of large-scale clinical trial data. This article reports a case of NSCLC with a rare BRAF insertion and deletion mutation that responded well to the treatment of Dabrafenib in combination with Trametinib, aiming to enhance clinicians' understanding of such NSCLC cases with extremely rare mutation and provide a reference for future treatment strategies.
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18. [Clinical Progress and Prospects of Antibody-drug Conjugates in Advanced NSCLC].
Advances in targeted therapy and immunotherapy have significantly improved clinical outcomes for patients with advanced non-small cell lung cancer (NSCLC), reshaping treatment paradigms. However, most patients ultimately face drug resistance, with limited options for subsequent therapies and suboptimal treatment efficacy, presenting a prominent challenge in current clinical practice. Antibody-drug conjugates (ADCs), characterized by high efficacy and favorable safety profiles, have emerged as a promising therapeutic frontier in recent years. This systematic review provides a comprehensive overview of the latest advancements in ADCs-based therapies for lung cancer, alongside discussions of the prevailing challenges in this rapidly evolving domain.
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19. [Advances in Targeted Therapy for Advanced Non-small Cell Lung Cancer with HER2 Mutation].
Human epidermal growth factor receptor 2 (HER2) mutations play a role as a driver gene in non-small cell lung cancer (NSCLC). Patients with advanced NSCLC harboring HER2 mutations exhibit poor responses to conventional chemotherapy and immunotherapy, hence targeted therapies against HER2 are under extensive investigation. This review analyzes the biological characteristics of HER2, an overview of clinical trials for targeted therapy drugs, including monoclonal antibodies, tyrosine kinase inhibitors (TKIs), and antibody-drug conjugate, and research directions for drug resistance in NSCLC. Currently, Pyrotinib and Trastuzumab deruxtecan have been approved for the treatment of advanced NSCLC with HER2 mutations, suitable for patients who have failed standard therapy, which is far from meeting the clinical demands. Novel selective HER2 TKIs are gradually emerging. Future exploration trends are gradually shifting from single drugs to combination strategies, and are exploring more precise selection strategies as well as research on resistance mechanisms. These studies will provide a theoretical basis for clinical treatment strategies for advanced NSCLC with HER2 mutations, promoting the development of personalized therapy.
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20. [Predicting Invasive Non-mucinous Lung Adenocarcinoma IASLC Grading: A Nomogram Based on Dual-energy CT Imaging and Conventional Features].
作者: Kaibo Zhu.;Liangna Deng.;Yue Hou.;Lulu Xiong.;Caixia Zhu.;Haisheng Wang.;Junlin Zhou.
来源: Zhongguo Fei Ai Za Zhi. 2025年28卷8期585-596页
Lung adenocarcinoma is an important pathohistologic subtype of non-small cell lung cancer (NSCLC). Invasive non-mucinous pulmonary adenocarcinomas (INMA) tend to have a poor prognosis due to their significant heterogeneity and diverse histologic components. Establishing a histologic grading system for INMA is crucial for evaluating its malignancy. In 2021, the International Association for the Study of Lung Cancer (IASLC) proposed that a new histological grading system could better stratify the prognosis of INMA patients. The aim of this study was to establish a visualized nomogram model to predict INMA IASLC grading preoperatively by means of dual-energy computed tomography (DECT), fractal dimension (FD), clinical features and conventional CT parameters.
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