Mean nuclear volume in squamous cell carcinoma of the vulva

OBJECTIVE: To compare mean nuclear volume (MNV) estimated by the stereologic intercept method in lymph node-positive and -negative cases of squamous cell carcinoma of the vulva. STUDY DESIGN: This retrospective study consisted of 53 cases (lymph node metastasis, n = 19; cases without lymph node metastasis, n = 34) of squamous cell carcinoma of the vulva. MNV was estimated with the help of an image cytometer. The nuclear point intersection method was used to measure MNV. The mean nuclear volumes of both lymph node-positive and -negative cases were compared. RESULT: MNV in the lymph node-negative and -positive cases was 717.0 +/- 533.1 and 1,961.4 +/- 1,369.6 microns 3, respectively (P < .000, Mann-Whitney U test). There was a significant difference in MNV between the 2 groups of tumors. CONCLUSION: The observations from the present study suggest that estimation of MNV of malignant squamous cells from the vulva on conventional histopathology sections may provide an objective and useful diagnostic tool in predicting lymph node metastasis.     

Mean nuclear volume in cervical intraepithelial neoplasia and carcinoma

OBJECTIVE: To correlate three-dimensional nuclear size (mean nuclear volume) estimated by the stereologic intercept methodfor objective classification of cervical intraepithelial neoplasia (CIN) and carcinoma. STUDY DESIGN: In this retrospective study a total number of 29 CIN cases (8 cases of CIN 1, 10 cases of CIN 2 and 11 cases of CIN 3) and 10 cervical squamous cell carcinoma cases were selected. Mean nuclear volume (MNV) of all cases was measured with an image cytometer (Leica, Cambridge, England) using Quantimet 600 software (Leica). Nuclear point resection method was adopted to measure nuclear volume. Mean intercepted diameter of at least 50 nuclei was measured randomly. MNV was correlated with the histologic grade and diagnosis. RESULTS: MNV of CIN 1, 2, 3 and carcinoma cases was 291.72, 403.33, 711.45 and 893 microm3, respectively. ANOVA test results showed that MNV of CIN 1 and 2 was significantly lower than that of CIN 3 and invasive carcinoma (P < .000). MNV of CIN 3 was also significantly lower than that of carcinoma cases (P <.05). CONCLUSION: The findings suggest that estimates of MNV on conventional histopathology slides provide objective and useful criteria for relatively subjective histopathologic grading.     

N-cadherin在卵巢癌中的表达及其临床病理意义

目的:探讨N-cadherin在人类卵巢癌组织中的表达及其临床-病理意义。方法:采用免疫组织化学染色法检测281例卵巢癌患者肿瘤组织中N-cadherin的表达,并分析其与患者临床病理特征之间的关系。结果:N-cadherin在卵巢癌原发灶中的表达显著低于配对的转移灶(P=0.018);卵巢癌组织中N-cadherin的表达与患者FIGO分期(P=0.034)、组织学类型(P0.001)、肿瘤分级(P=0.004)均显著相关。结论:N-cadherin高表达更多见于进展期(FIGOⅡ-Ⅳ)卵巢癌、高级别浆液性癌及高级别卵巢癌,可能与卵巢癌细胞的侵袭及迁移能力呈正相关,对判断卵巢癌的生物学行为具有重要的参考价值。     

Volume-weighted mean nuclear volume. Is this new prognosticator comparable in different institutions?

OBJECTIVE: To determine whether volume-weighted mean nuclear volume (MNV) obtained at one institution is comparable to that from other institutions. STUDY DESIGN: MNV calculated from histologic slides obtained at three hospitals--Shizuoka Prefectural Hospital (SPH), Shimada Municipal Hospital (SMH) and Shizuoka City Hospital (SCH)--were compared. Between December 1994 and June 1996, transurethral resection of bladder tumor or transurethral resection of the prostate was performed on 37 patients at SPH and 50 patients at SMH; histologic specimens from 40 cases of bladder tumors, 63 cases of normal bladder mucosa, 28 cases of benign prostatic hyperplasia and 1 case of prostate cancer were obtained. A portion of each specimen obtained at SPH or SMH was carried to SCH, and histologic slides were made at SCH using it. Using the remaining position of each specimen, histologic slides were then prepared at each hospital. Estimates of MNV were made from all histologic slides from each hospital, and the differences in MNV between the hospitals were analyzed. In addition, intraobserver and interobserver reproducibility were analyzed using 50 specimens obtained between December 1994 and August 1995. RESULTS: On linear regression analysis, comparison of MNVs calculated from the histologic slides from SPH and SCH and those calculated from SMH and SCH revealed high correlation coefficients (R = .966 and .966, respectively), and the slope of the regression line did not differ significantly from unity. The paired t test also disclosed no significant difference between MNVs calculated at the two hospitals. Furthermore, the correlation coefficients for intraobserver and interobserver reproducibility of MNV estimates were also high (R = .918 and .949, respectively). CONCLUSION: The results of this study indicate that estimates of MNV are comparable in multiple institutions, and we recommend that they be used to support subjective histologic grading.     

Infiltrating micropapillary carcinoma of the breast. Cytologic findings

OBJECTIVE: To examine the cytologic features of infiltrating micropapillary carcinoma (IMPC). METHODS: Using the histopathology files of one of the authors (I.J.B.), we retrospectively identified 20 IMPC cases (pure, 12; partial micropapillary carcinoma differentiation, 8) with corresponding cytology. We evaluated the cases for cellularity, atypia, architecture and background. RESULTS: All cases were diagnostic of malignancy, characterized by atypical cells present predominantly in three-dimensional clusters and single cells, facilitating the diagnosis. The clusters had cell ball and papillarylike arrangements, like the morular growth pattern seen on histopathology. Apocrine cytology was present in 12 cases, focal mucin background in 5 and psamomma bodies in 2. The differential diagnosis includes primary papillary neoplasms of the breast, metastatic ovarian papillary serous carcinoma, apocrine and colloid carcinoma of the breast, and intraductal carcinoma (micropapillary type). CONCLUSION: As in histopathology, the cytologic features of IMPC are unique and should be recognized due to its aggressive behavior.     

A Broadly Reactive One-Step SYBR Green I Real-Time RT-PCR Assay for Rapid Detection of Murine Norovirus

A one-step SYBR Green I real-time RT-PCR assay was developed for the detection and quantification of a broad range of murine noroviruses (MNVs). The primer design was based on the multiple sequence alignments of 101 sequences of the open reading frame (ORF)1−ORF2 junction of MNV. The broad reactivity and quantitative capacity of the assay were validated using 7 MNV plasmids. The assay was completed within 1 h, and the reliable detection limit was 10 copies of MNV plasmid or 0.063 median tissue culture infective doses per milliliter of RAW264 cell culture-propagated viruses. The diagnostic performance of the assay was evaluated using 158 mouse fecal samples, 91 of which were confirmed to be positive. The melting curve analysis demonstrated the diversity of MNV in the samples. This is the first report of a broadly reactive one-step SYBR Green I real-time RT-PCR assay for detecting of MNVs. The rapid and sensitive performance of this assay makes it a powerful tool for diagnostic applications.     

Ki-67 immunostaining and stereologic estimation of nuclear volume in melanocytic skin tumors

OBJECTIVE: To investigate the proliferative activity and mean nuclear volume (MNV) of melanocytic skin tumors. STUDY DESIGN: Proliferative activity, assessed by immunostaining for the Ki-67 monoclonal antibody (reactive with all actively cycling cells), and MNV, estimated by means of a stereologic method, were determined in 60 cutaneous melanocytic tumors, including 28 primary malignant melanomas (PMM), 13 compound nevi (CN), 11 dysplastic nevi and 8 metastatic malignant melanomas. RESULTS: Both MNV and Ki-67 expression differed significantly between CN and other melanocytic tumors and showed a good correlation with Clark's level (a well-established prognostic parameter in PMM). CONCLUSION: The association of proliferative activity and quantitative nuclear features may be helpful in the interpretation of the degree of malignancy in melanocytic skin tumors.     

Expression of nucleolar organizer regions (NORs) in ovarian epithelial tumors

AgNOR staining technique was tested in ovarian epithelial tumors to evaluate its diagnostic potential in distinguishing between borderline tumors and well-differentiated carcinomas. In our opinion, the AgNOR count appears useful for assessing differences only between borderline and well-differentiated serous ovarian tumors at stage I of FIGO clinical advancement.     

复发卵巢成人型颗粒细胞瘤的临床特点及复发的影响因素分析

摘要 目的：探讨复发卵巢成人型颗粒细胞瘤（AGCT）的临床特点及复发的影响因素。方法：回顾性分析我院收治的24例复发AGCT患者的临床资料。结果：2014年1月-2021年12月在四川大学华西第二医院共收治卵巢成人型颗粒细胞瘤的患者97例,复发AGCT患者24例,复发率24.7 %。初次复发距离初次治疗的中位间隔时间为69个月（24月-144月）。24例复发AGCT初发平均年龄42.8岁（24岁-60岁）。初诊时肿瘤最大直径<10 cm 15例,肿瘤最大直径≥10 cm 9例。初次FIGO分期：I期14例,占58.3 %,II期3例,占12.5 %,III期7例,占29.1 %。I期患者中肿瘤破裂8例。所有病例初次治疗时均接受手术治疗。保留生育功能手术8例,接受非保留生育功能的手术16例。初次手术后14例患者接受了化疗,其中I期患者14例,有4例接受辅助化疗,有10例术后未接受辅助化疗。复发后有7例患者发生多次复发。Cox回归模型分析显示FIGO分期、I期患者肿瘤破裂为导致复发卵巢成人型颗粒细胞瘤复发的危险因素（P<0.05）。结论：AGCT为低度恶性肿瘤,有远期复发和多次复发的风险,FIGO分期是影响复发的因素,晚期的患者更易复发。对于部分临床早期患者,肿瘤破裂也会增加复发的风险。AGCT患者需长期随访。     

宫颈癌患者四维能量多普勒超声血管血流参数与疾病分期的相关性分析

摘要 目的：探究宫颈癌患者四维能量多普勒超声血管血流参数与其疾病分期的相关性。方法：选择2019年8月至2022年7月于我院接受治疗的80例确诊为宫颈癌患者为研究组,另取同期入院检测的50例宫颈癌上皮内瘤变患者为CIN组,取同期确诊为子宫良性病变的50例患者为对照组,分别对其进行了四维能量多普勒超声检测,对比三组患者超声参数差异,将研究组患者按照FIGO标准区分为不同疾病分期（I期23,II期34,III期23）,对比不同分期宫颈癌患者超声参数差异,通过绘制受试者曲线（ROC）的方式评估超声参数对不同宫颈癌分期的鉴别价值。结果：研究组、CIN组和对照组之间超声血流参数PSV及RI存在显著差异,同时两两相比较同样组间差异具有统计学意义（P<0.05）;不同宫颈癌分期患者超声血流参数之间存在显著差异,以FIGO III期的PSV最高,RI最低,各组两两相比较同样差异具有统计学意义（P<0.05）;PSV对FIGO I期至FIGO II期诊断AUC为0.6829（95% CI=0.5333-0.8324,P=0.0200）,对FIGO II期至FIGO III期诊断AUC为0.7698（95% CI=0.6402-0.8995,P=0.0006）,对FIGO I期至FIGO III期诊断AUC为0.7505（95% CI=0.6072-0.8937,P=0.0036）;RI对FIGO I期至FIGO II期诊断AUC为0.9309（95% CI=0.8662-0.9957,P<0.0001）,对FIGO II期至FIGO III期诊断AUC为0.7148（95% CI=0.5804-0.8493,P=0.0063）,对FIGO I期至FIGO III期诊断AUC为0.9811（95% CI=0.9504-1.000,P<0.0001）。结论：宫颈癌患者四维能量多普勒超声血管血流参数与其疾病分期具有一定的关联,将PSV和RI指数应用于宫颈癌分期鉴别中具有较好的应用价值,具有推广应用意义。     

Segregation of ovarian cancer stage exploiting spectral biomarkers derived from blood plasma or serum analysis: ATR‐FTIR spectroscopy coupled with variable selection methods

Ovarian cancer is a solid tumor and a leading cause of mortality. Diagnostic tools for the detection of early stage (stage I) ovarian cancer are urgently needed. For this purpose, attenuated total reflection Fourier‐transform infrared spectroscopy (ATR‐FTIR) coupled with variable selection methods, successive projection algorithm or genetic algorithm (GA) combined with linear discriminant analysis (LDA), were employed to identify spectral biomarkers in blood plasma or serum samples for accurate diagnosis of different stages of ovarian cancer, histological type and segregation based on age. Three spectral datasets (stage I vs. stage II–IV; serous vs. non‐serous carcinoma; and, ≤60 years vs. >60 years) were processed: sensitivity and specificity required for real‐world diagnosis of ovarian cancer was achieved. Toward segregating stage I vs. stage II–IV, sensitivity and specificity (plasma blood) of 100% was achieved using a GA‐LDA model with 33 wavenumbers. For serous vs. non‐serous category (plasma blood), the sensitivity and specificity levels, using 29 wavenumbers by GA‐LDA, were remarkable (up to 94%). For ≤60 years and >60 years categories (plasma blood), the sensitivity and specificity, using 42 wavenumbers by GA‐LDA, gave complete accuracy (100%). For serum samples, sensitivity and specificity results gave relatively high accuracy (up to 91.6% stage I vs. stage II–IV; up to 93.0% serous vs. non‐serous; and, up to 96.0% ≤60 years vs. >60 years) using several wavenumbers. These findings justify a prospective population‐based assessment of biomarkers signatures using ATR‐FTIR spectroscopy as a screening tool for stage of ovarian cancer. © 2015 American Institute of Chemical Engineers Biotechnol. Prog., 31:832–839, 2015     

Peritoneal washings in ovarian tumors. Potential sources of error in cytologic diagnosis

Peritoneal washings were performed on 48 patients with suspected or known ovarian carcinoma. The procedure was part of the initial surgical staging in 27 patients with presumed stage I and II ovarian cancer and was performed during second-look operations in 21 other cases with proven ovarian malignancy. This paper presents the microscopic features of the washings, with particular emphasis on the cytologic differentiation between benign and malignant findings outside of the ovary. Thirty-four cases showed benign or reactive mesothelial cells and no evidence of peritoneal disease. The washings of six patient showed malignant cells, which were confirmed histologically. Notable atypia that mimicked ovarian carcinoma was found in eight patients who had benign or borderline lesions. These findings included papillary and glandlike epithelial structures, with varying degrees of cellular atypia and psammoma bodies. The histologic counterparts of these atypicalities were Müllerian inclusions, mesothelial proliferations and borderline serous tumors. The differential diagnosis between these entities is essential because false-positive cytologic diagnoses may alter postoperative treatment in some patients.     

Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma

In epithelial ovarian cancer, the high mortality rate is usually ascribed to late diagnosis, since these tumors commonly lack early-warning symptoms, but tumor-associated biomarkers useful for prognosis or therapy response prediction are in short supply. However, members of the tissue kallikrein serine protease family, the serine protease uPA and its inhibitor PAI-1, are associated with tumor progression of ovarian cancer. Therefore, we used ELISA to determine uPA, PAI-1, and tissue kallikreins hK5-8, 10, 11, and 13 in extracts of 142 primary tumor tissue specimens from ovarian cancer patients and studied the strength of association between protein expression levels of these tumor tissue-associated factors. uPA, PAI-1, hk5, and hk8 were related to FIGO stage; hK5 expression was higher in FIGO III/IV than in FIGO I/II patient tissues. PAI-1 and hk5 differed significantly according to nuclear grading; expression of hK5 was higher in G3 than in G1/2 tumors. Associations between uPA, PAI-1, and the tissue kallikreins were weak. There were strong pairwise correlations within the cluster of tissue kallikreins hK5, 6, 7, 8, 10, and 11, but their bivariate distributions depended on nuclear grading. These results support the notion that several tissue kallikreins are co-expressed in ovarian cancer patients, substantiating the existence of a steroid hormone-driven tissue kallikrein cascade in this disease.     

New insights on the pathogenesis of ovarian carcinoma: molecular basis and clinical implications

Ovarian carcinoma can be subdivided into two categories termed type I and type II. Type I tumours, usually having an indolent clinical behaviour, are often detected in early stage, and rarely harbour p53 gene mutations. Each histological type has a distinct molecular profile with mutations of genes involved in different signalling transduction pathways, such as KRAS, BRAF, CTNNB1, PTEN, PIK3CA and ARID1A. Type II tumours, accounting for 75% of the cases, have a very aggressive biological behaviour, are usually in advanced stage at presentation, harbour p53 gene mutations in 80% of the cases, and sometimes have alterations of homologous recombination (HR). Both type I and type II tumours arise from extra-ovarian precursors. Serous carcinomas derive from tubal epithelium, endometrioid and clear cell carcinomas from endometrial tissue, and mucinous and Brenner tumours from transitional epithelial cells located near the tubo-peritoneal junction. These new concepts on the pathogenesis of ovarian carcinoma could deeply modify both the preventive approach in women with germ-line BRCA(1) or BRCA(2) mutations and the treatment of patients with advanced or recurrent disease. For instance, BRAF inhibitors could be used in low-grade serous carcinomas, PIK3CA inhibitors could be employed in clear cell carcinoma, and poly (ADP-ribose) polymerase inhibitors could be used not only in hereditary ovarian carcinoma but also in non-hereditary, high-grade serous ovarian carcinoma which sometimes shows defective HR.     

Usefulness of endometrial aspiration cytology for the preoperative diagnosis of ovarian carcinoma

OBJECTIVE: To evaluate the usefulness of endometrial aspiration cytology for the preoperative diagnosis of ovarian carcinoma. STUDY DESIGN: A total of 210 patients with ovarian carcinoma were investigated by endometrial aspiration cytology. RESULTS: Fifty-five of 210 patients (26.2%) had positive endometrial aspiration cytology. The positive rates of endometrial cytology were 3.9% in stage I, 23.8% in stage II, 36.5% in stage III and 53.3% in stage IV. When classified by histologic type, the positive rates of endometrial cytology in patients with serous adenocarcinoma, mucinous adenocarcinoma, clear cell adenocarcinoma, undifferentiated carcinoma and yolk sac tumor were 38.9%, 11.8%, 21.1%, 16.7% and 16.7%, respectively. One hundred twenty-eight of 210 patients (61.0%) were positive on peritoneal cytology, and 54 of these 128 cases (42.2%) were also positive on endometrial cytology. The positive rates of endometrial cytology were especially high in patients with serous adenocarcinoma (51.2%) and those with clear cell adenocarcinoma (40.0%) among those who were positive on peritoneal cytology. Of 74 patients who were negative on peritoneal cytology, only one (1.4%) with mucinous adenocarcinoma had positive endometrial cytology. Hysterectomy was performed on 130 patients, and the positive rate of endometrial cytology was 100% in 4 patients with endometrial invasion and 15.9% in 126 cases without invasion. CONCLUSION: Endometrial aspiration cytology can detect ovarian carcinoma cells not only in patients with endometrial involvement but also in patients with positive peritoneal cytology. Endometrial aspiration cytology appears to be useful for the preoperative diagnosis of ovarian carcinoma.     

Angiotensin II reverses the inhibitory action produced by theca cells on bovine oocyte nuclear maturation

The presence of prorenin, renin, angiotensinogen, angiotensin-converting enzyme, angiotensin II (Ang II) and Ang II receptors in the ovary is suggestive of a functional ovarian renin-angiotensin system (RAS). In cattle, the expression of Ang II is greatest in large follicles, suggesting that it is important during follicular growth and maturation. The present study was designed to investigate the role of Ang II in bovine oocyte nuclear maturation. Bovine cumulus-oocyte complexes (COCs) were cultured with or without follicular cells and Ang II or saralasin (Ang II antagonist). In the absence of follicular cells, Ang II at 0, 10(-11), 10(-9) and 10(-7) M did not affect the percentage of oocytes reaching the germinal vesicle breakdown (GVBD), metaphase I (MI) and metaphase II (MII) stage after 7-h (41.3 +/- 4.3, 35.3 +/- 4.0, 31.3 +/- 9.7, 38.7 +/- 8.6), 12-h (31.6 +/- 7.0, 34.7 +/- 6.1, 31.7 +/- 5.3, 28.9 +/- 9.1; mean +/- S.E.M.) and 18-h (44.9 +/- 7.3, 58.4 +/- 8.4, 53.1 +/- 7.4, 44.9 +/- 7.3) of culture, respectively. Similarly, saralasin at 0, 10(-11), 10(-9) and 10(-7) M did not affect the percentage of oocytes reaching MII stage after 18-h of culture (37.6 +/- 7.4, 34.4 +/- 7.7, 30.0 +/- 10.8 and 31.2 +/- 5.1, respectively). The theca cells (MII = 22.9%) or medium conditioned with follicular cells (GV = 65.5%, MI = 23.6%) inhibited oocyte maturation; however, theca cells (MII = 35.5 +/- 4.9; P < 0.05) or medium conditioned with follicular cells (GV = 34.6%, MI = 52.7%; P < 0.01) were not able to inhibit nuclear maturation when Ang II (10(-11) M) was present in the culture system. Theca cells remained viable during the culture period when Ang II was present. Therefore, results supported the idea of a role of Ang II in blocking the inhibitory effect of theca cells on nuclear maturation of bovine oocytes.     

Peritoneal washings in endometrial carcinoma. A study of 298 patients with histopathologic correlation

OBJECTIVE: To correlate findings of peritoneal washings in patients with endometrial carcinoma with histologic parameters. STUDY DESIGN: Between 1995 and 1998, 298 women with endometrial carcinoma were treated by hysterectomy with intraoperative peritoneal washings (PW) at Memorial Sloan-Kettering Cancer Center. All cytology and pathology slides were available for review. Pathologic parameters of hysterectomy specimens were evaluated and correlated with the findings of PW. RESULTS: Thirty-two patients (10.7%) had abnormal PW. Two hundred sixty-two had endometrioid adenocarcinoma; 26 of them had abnormal PW (10.0%). Thirty-six patients had other histologic subtypes (papillary serous carcinoma, clear cell carcinoma and adenosquamous carcinoma), and six of them had abnormal PW (16.7%). The incidence of abnormal PW in the two groups was not significantly different (P = .78). Among 26 patients with endometrioid adenocarcinoma and abnormal PW, there were 17 cases (9.9%) of International Federation of Gynecology and Obstetrics (FIGO) grade 1, 7 (12.7%) of grade 2 and 2 (5.7%) of grade 3 (P = .56). Ten cases (14.9%) had no myometrial invasion, 10 (7.0%) had myometrial invasion of < or = 50% of myometrial thickness, and 6 (11.5%) had invasion of > 50% of myometrial thickness (P = .18). Vascular invasion was present in 8 cases (14.8%) and absent from 17 (8.2%) (P = .14). Eighteen patients (7.6%) had stage I/II disease, and eight patients (30.8%) had stage III/IV disease (P = .001). Among 298 patients, cervicovaginal smears performed before surgery were available for review in 76. Five of the 7 patients (71.4%) with abnormal PW and 37 of the 69 patients (53.6%) with normal PW had abnormal Pap smears (P = .45). CONCLUSION: Abnormal PW did not correlate with histologic subtypes, FIGO grade, depth of myometrial invasion, vascular invasion or abnormal Pap smears. A significantly higher incidence of abnormal PW was associated with stage III/IV disease.     

Utility of mean nuclear volume in predicting disease-free survival in locally advanced invasive cervical squamous cell carcinoma

OBJECTIVE: To evaluate mean nuclear volume (MNV) as a prognostic indicator in invasive squamous cell carcinoma of the uterine cervix. STUDY DESIGN: Forty-nine consecutive cases of invasive squamous cell carcinoma of the cervix diagnosed in 1995 were analyzed retrospectively for MNV and correlated with outcome at the end of a 5-year follow-up period. RESULTS: The average MNV among patients with a 5-year disease-free survival (DFS) and patients with disease recurrence within the same period was 1424.11 microm3 and 1401.49 microm3, respectively (P = .984, Mann-Whitney test), indicating a poor relationship between MNV and 5-year DFS. CONCLUSION: Estimation of MNV alone in cases of invasive squamous cell carcinoma of the cervix is not predictive of DFS.