1.Biological characteristics of spontaneous ovarian cancer in Microtusfortis.
Junkang ZHOU ; Tianqiong HE ; Yixin WEN ; Qian LIU ; Wenling ZHI ; Lingxuan OUYANG ; Yushan QI ; Xin GAO ; Zikang ZHOU ; Zhijun ZHOU
Journal of Central South University(Medical Sciences) 2025;50(1):11-22
OBJECTIVES:
Wild-caught Microtus fortis (M. fortis) at the age of 9-15 months can develop epithelial ovarian cancers similar to human epithelial ovarian cancers under natural conditions during experimental animal breeding, but its pathological types and biological characteristics remain unclear. This study aims to analyze the biological characteristics of spontaneous ovarian cancer in M. fortis, intending to develop M. fortis as an animal model for human epithelial ovarian cancer.
METHODS:
The female M. fortis (9-15 months old) with spontaneous ovarian cancer were selected as the experimental group, and healthy M. fortis from the same litter were selected as the control group. The ovarian pathological changes of the two groups were observed by dissection. Blood routine and biochemical indicators were measured by biochemical analysis. Hematoxylin and eosin (HE) staining was performed to observe the pathological changes in the ovarian cancer tissue of M. fortis. Immunohistochemical staining was used to detect the protein expression of common ovarian cancer markers, and real-time RT-PCR was used to analyze the transcription levels of ovarian cancer-related genes.
RESULTS:
Spontaneous ovarian cancer in M. fortis mainly affects both ovaries, with tumors appearing solid or cystic. HE staining and histopathological analysis confirmed that the ovarian tumors originated from ovarian surface epithelium. Compared to the control group, the experimental group showed significantly decreased hemoglobin (P<0.01), hematocrit (P<0.05), albumin (P<0.05), and blood glucose levels (P<0.01), while lymphocyte percentage (P<0.05), monocyte percentage (P<0.05), cholesterol (P<0.01), and progesterone (P<0.01) levels were significantly increased. Expression of ovarian cancer-related genes, including ID3, CDC42, RHOA, RB1CC1, NF1, PIN1, MIB1, PDS5A, MCM7, and MLH1, was significantly downregulated (all P<0.05), while PAX8 gene expression was significantly upregulated (P<0.05). Immunohistochemical results showed that Wilms' tumor gene 1 (WT1) protein was mainly distributed throughout the cell, with significantly higher expression in ovarian cancer M. fortis. Tumor protein 53 (TP53) was expressed in both healthy and ovarian cancer M. fortis and was distributed throughout the cell. Hepatocyte nuclear factor 1 beta (HNF1B) and progesterone receptor (PR) protein were highly expressed in the ovarian tissue of healthy M. fortis but were significantly reduced in the ovarian cancer M. fortis, though both were located in the cytoplasm.
CONCLUSIONS
Spontaneous ovarian cancer in M. fortis is serous ovarian cancer. Compared to healthy M. fortis, significant differences were observed in ovarian tissue morphology, biochemical indicators, ovarian cancer-related gene expression, and protein expression, which show similarity to the biological characteristics of human serous ovarian cancer. This suggests that M. fortis could be an ideal animal model for studying human serous ovarian cancer.
Female
;
Ovarian Neoplasms/metabolism*
;
Animals
;
Carcinoma, Ovarian Epithelial
;
Disease Models, Animal
;
Humans
;
Neoplasms, Glandular and Epithelial/metabolism*
;
Ovary/pathology*
2.Significance of TERT promoter mutation in differential diagnosis of non-invasive inverted urothelial lesions of bladder.
Y H ZHANG ; J J XIE ; J G WANG ; Y WANG ; X H ZHAN ; J GAO ; H Y HE
Chinese Journal of Pathology 2023;52(12):1216-1222
Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.
Humans
;
Urinary Bladder Neoplasms/genetics*
;
Carcinoma, Transitional Cell/pathology*
;
Urinary Bladder/pathology*
;
Diagnosis, Differential
;
Retrospective Studies
;
Mutation
;
Cystitis/genetics*
;
Neoplasms, Glandular and Epithelial/diagnosis*
;
Papilloma/diagnosis*
;
Telomerase/genetics*
3.Clinicopathological and genetic characteristics of bronchial sialadenoma papilliferum: report of four cases.
Lin LIANG ; Chun Yan WU ; Li Ping ZHANG ; Li Kun HOU ; Zheng Wei DONG ; Wei WU ; Jie Lu LIN ; Yan HUANG ; Hui Kang XIE
Chinese Journal of Pathology 2022;51(3):212-217
Objective: To investigate the clinicopathological, immunophenotypic, and molecular genetic features of bronchial sialadenoma papilliferum (BSP). Methods: Four cases of BSP collected at the Shanghai Pulmonary Hospital from May 2018 to June 2021 were retrieved and analyzed. These cases were evaluated for their clinical, histological, immunohistochemical (IHC) and genomic features. The patients were followed up and relevant literature was reviewed. Results: All four patients were male, aged from 55 to 75 years (mean 62 years), with tumor diameter of 6 to 21 mm (mean 13.5 mm), and lesions were located in the left lower lobe (n=2), right lower lobe (n=1), and trachea (n=1). They were characterized by a combination of surface exophytic endobronchial papillary proliferation and an endophytic two-cell layered ductal structure. IHC staining showed that CK7 and EMA were strongly positive in ductal epithelium; p63, p40, CK5/6 were positive in ductal and papillary basal cells; SOX10 was positive in ductal epithelium and basal cells; S-100 was positive in basal cells and ductal epithelium in two cases. Next generation sequencing showed that two cases harbored BRAF V600E mutation. Conclusions: BSP is an extremely rare primary lung tumor arising from the salivary gland under bronchial mucosa. The primary treatment choice of this tumor is complete surgical resection. The diagnosis and differential diagnosis of this tumor depend on classic histomorphologic and IHC features, and BRAF V600E gene mutation can be detected.
Aged
;
China
;
Epithelium/pathology*
;
Humans
;
Immunohistochemistry
;
Male
;
Middle Aged
;
Neoplasms, Glandular and Epithelial/pathology*
;
Salivary Gland Neoplasms/surgery*
5.Correlation between Serum Cytokeratin 19 Fragment and the Clinicopathological Features and Prognosis of Thymic Epithelial Tumors.
Xuefei ZHANG ; Chunyu JI ; Zhitao GU ; Wentao FANG
Chinese Journal of Lung Cancer 2018;21(7):519-525
BACKGROUND:
So far there's no tumor maker applied in diagnosis and treatment of thymic epithelial tumors. This study is to assess the correlation between serum cytokine 19 fragment (Cyfra 21-1) and clinicopathological features and prognosis of thymic epithelial tumors (TETs).
METHODS:
The clinical data of 159 patients with TETs in Shanghai Chest Hospital was retrospectively analysed. Patients were divided into groups according to different tumor stages and histotypes. Serum Cyfra 21-1 was thus compared. In addition, the possible relationship between perioperative serum Cyfra 21-1 level and the recurrent status was carrid out.
RESULTS:
Preoperative Cyfra 21-1 serum concentrations in patiants with advanced stage (T4) and thymic carcinomas were significantly higher than that in others (P<0.001, P<0.001, respectively). When the preoperative serum level exceeds the out-off of 1.66 ng/mL, it possibly indicates the recurrence during follow up. Furthermore, the sensitivity, specificity, and positive as well as negative predictive value (PPV and NPV) of postoperative Cyfra 21-1 to predict tumor recurrence were evaluated. At a cut-off of Cyfra 21-1 of 2.66 ng/mL, the sensitivity was 0.7, the specificity was 0.925, the PPV was 0.5 and the NPV was 0.966.
CONCLUSIONS
The elevated level of preoperative serum Cyfra 21-1 indicates an advanced stage of tumor or a more malignant histotype (thymic carcinoma). It also probably suggests a higher risk of tumor recurrence. During the oncological follow up, in addition to regular imaging examinations, the blood test of serum Cyfra 21-1 is also suggested to improve the diagnosis of tumor recurrence in order to improve the prognosis.
Biomarkers, Tumor
;
blood
;
Female
;
Follow-Up Studies
;
Humans
;
Keratin-19
;
blood
;
chemistry
;
Male
;
Middle Aged
;
Neoplasms, Glandular and Epithelial
;
blood
;
diagnosis
;
pathology
;
Peptide Fragments
;
blood
;
Prognosis
;
ROC Curve
;
Retrospective Studies
;
Thymus Neoplasms
;
blood
;
diagnosis
;
pathology
6.Negative pathology after endoscopic resection of gastric epithelial neoplasms: importance of pit dysplasia.
Joon Hyung JHI ; Gwang Ha KIM ; Ahrong KIM ; Young Geum KIM ; Cheong Su HWANG ; Sojeong LEE ; Bong Eun LEE ; Geun Am SONG ; Do Youn PARK
The Korean Journal of Internal Medicine 2017;32(4):647-655
BACKGROUND/AIMS: Endoscopic resection (ER) is a well-established treatment modality for gastric epithelial neoplasm. However, there is a discrepancy between forceps biopsy and ER specimen pathology, including a negative pathologic diagnosis (NPD) after ER. It has been suggested that pit dysplasia (PD) is a subtype of gastric dysplasia, and the aim of this study was to assess the significance of PD in cases with NPD after ER for early gastric neoplasms. METHODS: After ER, 29 NPD lesions that had an associated pretreatment forceps biopsy specimen, were correctly targeted during ER, and had no cautery artifact on the resected specimen were included in this study. RESULTS: Sixteen lesions showed PD and 13 had no neoplastic pathology. The initial pretreatment forceps biopsy diagnoses of 29 NPD lesions were low-grade dysplasia (LGD) in 17 lesions, high-grade dysplasia (HGD) in seven lesions, and adenocarcinoma in five lesions, which after review were revised to PD in 19 lesions, LGD in four lesions, adenocarcinoma in two lesions, and no neoplastic pathology in four lesions. Overall, nine lesions (31%) were small enough to be removed by forceps biopsy, four NPD lesions (14%) were initially misinterpreted as neoplastic lesions, and 16 PD lesions (55%) were misinterpreted as NPD lesions on ER slides. CONCLUSIONS: Approximately half of the lesions initially diagnosed as LGD or HGD were subsequently classified as PD. Therefore, including PD as a subtype of gastric dysplasia could reduce the diagnostic discrepancy between initial forceps biopsy and ER specimens.
Adenocarcinoma
;
Artifacts
;
Biopsy
;
Cautery
;
Diagnosis
;
Neoplasms, Glandular and Epithelial*
;
Pathology*
;
Stomach
;
Stomach Neoplasms
;
Surgical Instruments
7.Analysis of prognostic factors of 110 patients with metastatic ovarian tumors from gastric cancer.
Zhenchi MA ; Rupeng ZHANG ; Qiang XUE ; Han LIANG
Chinese Journal of Gastrointestinal Surgery 2016;19(3):287-291
OBJECTIVETo explore the clinicopathalogical features, treatment methods and prognostic factors of metastatic ovarian tumors from gastric cancer.
METHODClinical data of 110 gastric cancer patients with metastatic ovarian tumor between January 2001 and August 2015 of Tianjin Medical University Cancer Institute and Hospital were reviewed retrospectively. Univariate and Cox regression model multivariate analyses were performed to investigate the risk factors of metastatic ovarian tumor from gastric cancer.
RESULTThe follow-up duration ranged from 3 to 60 months (mean 12 months). The follow-up rate was 94.5%(104/110). 104 cases underwent surgical treatment, including satisfactory cytoreductive surgery (57 cases) and unsatisfactory cytoreductive surgery (47 cases). The median overall survival was 12 months and median progression-free survival was 8 months. The survival rates of 1-, 3- and 5-year were 48.1%, 7.7% and 0, respectively. Univariate analysis revealed that pattern of metastasectomy, number of metastatic lymph node, cytoreductive surgery level, presence of peritoneal metastasis or not when ovarian metastasis was diagnosed, ovariectomy prior to primary gastric cancer and extent of ovarian metastatic lesion were associated with prognosis(P<0.05). Multivariate analysis revealed that extent of ovarian metastatic lesion(RR=2.76, 95% CI: 1.68 to 4.54, P=0.005), presence of peritoneal metastasis when ovarian metastasis was diagnosed (RR=0.21, 95% CI: 0.11 to 0.41, P=0.003) and cytoreductive surgery level(RR=3.67, 95% CI: 2.13 to 6.33, P=0.011) were independent prognostic factors.
CONCLUSIONSPrognosis of patients with metastatic ovarian carcinoma from gastric cancer is quite poor. Extent of ovarian metastatic lesion and peritoneal metastasis were independent prognostic factors. Optimal cytoreduction is associated with better survival.
Disease-Free Survival ; Female ; Humans ; Multivariate Analysis ; Neoplasms, Glandular and Epithelial ; diagnosis ; secondary ; Ovarian Neoplasms ; diagnosis ; secondary ; Prognosis ; Retrospective Studies ; Risk Factors ; Stomach Neoplasms ; pathology ; Survival Rate
8.Relationship between P53 Protein Expression and Prognosis of Advanced Ovarian Serous Adenocarcinoma.
Jing ZUO ; Yan SONG ; Zhuo LI ; Ling-ying WU
Acta Academiae Medicinae Sinicae 2016;38(2):169-174
OBJECTIVETo study the expression of P53 protein in the advanced ovarian serous adenocarcinoma and explore its potential correlation with the clinicopathological features and prognosis of ovarian cancer.
METHODSThe immunohistochemical staining was used to detect the expression of P53 protein in 183 patients with advanced ovarian serous adenocarcinoma. The correlation of P53 protein with the clinicopathological features and its significance in the assessment of prognosis were explored.
RESULTSThe P53 protein expression was positive in 62.8% of the patients. Chi-square test showed that the overexpression of P53 protein was positively correlated with the elevation of serum CA125 and the two-tier grading of ovarian serous adenocarcinoma (P<0.001, P=0.038). Univariate analysis suggested that the prognosis of patients was associated with two-tier grading (P=0.007), lymph node metastasis (P=0.036), preoperative serum CA125 level (P=0.002), and P53 overexpression (P<0.001). Multivariate analysis showed that the International Federation of Gynecology and Obstetrics stage (P=0.038), lymph node metastasis (P=0.002), and overexpression of P53 (P=0.001) were independent prognostic factors.
CONCLUSIONThe P53 protein expression is closely related to the prognosis of advanced ovarian serous adenocarcinoma and can be used as an important indicator for predicting the prognosis.
CA-125 Antigen ; blood ; Cystadenocarcinoma, Serous ; metabolism ; pathology ; Female ; Humans ; Lymphatic Metastasis ; Membrane Proteins ; blood ; Neoplasm Grading ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Ovarian Neoplasms ; metabolism ; pathology ; Prognosis ; Tumor Suppressor Protein p53 ; metabolism
9.Expressions of OCT4, Notch1 and DLL4 and their clinical implications in epithelial ovarian cancer.
Lan YU ; Yun-Jie JIAO ; Lei ZHOU ; Wen-Qing SONG ; Shi-Wu WU ; Dan-Na WANG
Journal of Southern Medical University 2016;37(4):444-450
OBJECTIVETo investigate the correlations among OCT4, Notch1 and DLL4 and their association with the clinicopathological features of patients with epithelial ovarian cancer (EOC).
METHODSA total of 207 specimens of EOC and 65 specimens of benign ovarian epithelial tumor tissues were examined for expressions of OCT4, Notch1 and DLL4 proteins using immunohistochemistry.
RESULTSThe positivity rates of OCT4, Notch1 and DLL4 in EOC tissues were 60.0%, 61.8% and 60.9%, respectively, significantly higher than the rates in benign epithelial tumor tissues (9.2%, 6.2%, and 0, respectively; P<0.05). The expressions of OCT4, Notch1 and DLL4 in EOC were significantly correlated with tumor differentiation, FIGO stage, and lymph node metastasis (P<0.05). DLL4 was positively correlated with OCT4 and Notch1 expressions (r=0.758 and 0.704, respectively, P<0.001), and the latter two were also positively correlated (r=0.645, P<0.001). Overexpressions of OCT4, Notch1 and DLL4 were associated with a poor prognosis, and the survival rate was significantly lower in patients positive for OCT4, Notch1, and DLL4 than in the negative patients (P<0.05). FIGO stage and expressions of OCT4 and DLL4 were independent prognostic factors of EOC (P<0.05).
CONCLUSIONThe expressions of OCT4, Notch1 and DLL4 are correlated with the differentiation, lymph node metastasis, clinical stage and prognosis of EOC. Combined detection of the 3 proteins has an important value in predicting the progression and prognosis of EOC.
Disease Progression ; Female ; Humans ; Immunohistochemistry ; Intercellular Signaling Peptides and Proteins ; metabolism ; Lymphatic Metastasis ; Neoplasms, Glandular and Epithelial ; metabolism ; pathology ; Octamer Transcription Factor-3 ; metabolism ; Ovarian Neoplasms ; metabolism ; pathology ; Prognosis ; Receptor, Notch1 ; metabolism ; Survival Rate
10.Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer.
Jin Young PARK ; Eun Jin HEO ; Jeong Won LEE ; Yoo Young LEE ; Tae Joong KIM ; Byoung Gie KIM ; Duk Soo BAE
Journal of Gynecologic Oncology 2016;27(2):e20-
OBJECTIVE: Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. METHODS: We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged < or =40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. RESULTS: A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. CONCLUSION: FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.
Adolescent
;
Adult
;
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
;
Female
;
*Fertility Preservation
;
Humans
;
Laparoscopy
;
Live Birth
;
Neoplasm Recurrence, Local/blood/diagnosis/*therapy
;
Neoplasm Staging
;
Neoplasms, Glandular and Epithelial/drug therapy/*pathology/*surgery
;
*Organ Sparing Treatments
;
Ovarian Neoplasms/drug therapy/*pathology/*surgery
;
Pregnancy
;
Pregnancy Rate
;
Retrospective Studies
;
Term Birth
;
Treatment Outcome
;
Young Adult

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