Role of serum microRNAs as biomarkers for endometriosis, endometrioid carcinoma of ovary & endometrioid endometrial cancer

Background & objectives: Accurate and early diagnosis is imperial in the management of endometriosis, endometrioid carcinoma of ovary (ECO) and endometrioid endometrial cancer (EC), yet there are no definitive diagnostic methods available for these diseases. Therefore, the present study was aimed to evaluate the diagnostic potential of differentially expressed miRNAs in serum samples of women with endometriosis, ECO and EC to establish them as diagnostic biomarkers. Methods: Blood samples (5 ml) were obtained from 40 patients (n=10/study group) undergoing laparoscopy/laparotomy/hysterectomy. miRNA-rich RNA was extracted from the serum samples, and quantitative real-time (qRT)-PCR was performed to check the expression levels of miR-16, miR-99b, miR-20a, miR-145, miR-143 and miR-125a in all the samples. Receiver operating characteristic (ROC) curve analysis was done to check the diagnostic potential. Results: In endometriosis, miR-16 was downregulated (P<0.05) whereas miR-99b, miR-125a, miR-143 and miR-145 were upregulated (P<0.05). In ECO group, downregulated expression of miR-16 and miR-125a (P<0.05) was observed, whereas miR-99b, miR-143 and miR-145 were upregulated (P<0.05). In endometrioid EC, miR-16, miR-99b, miR-125 and miR-145 were downregulated (P<0.05), whereas miR-143 was upregulated (P<0.05). ROC curve analysis showed that, for endometriosis, miR-99b, miR-125a, miR-143 and miR-145 served as diagnostic markers. miR-145 showed diagnostic power for ECO, and for endometrioid EC, miR-16, miR-99b, miR-125a and miR-145 showed diagnostic potential. Interpretation & conclusions: The present findings suggested that certain circulating miRNAs (miB99b, miR-16, miR-125a, miR-145) might act as indicators and discriminators of endometriosis and endometrioid subtypes of EC and ovarian cancer and might serve as potential biomarkers for early diagnosis and management of these debilitating diseases.

Secretory cell outgrowths, p53 signatures, and serous tubal intraepithelial carcinoma in the fallopian tubes of patients with sporadic pelvic serous carcinoma.

Context: High‑grade serous carcinomas of ovarian, tubal, and peritoneal origin are together referred as pelvic serous carcinoma. The fallopian tubes, ovarian surface epithelium, and the tuboperitoneal junctional epithelium are all implicated in pelvic serous carcinogenesis. Aims: The aim of this study is to identify putative precursor lesions of serous carcinoma including secretory cell outgrowths (SCOUTs), serous tubal intraepithelial carcinoma (STIC), and p53 signatures and assign its probable site of origin. Settings and Design: Prospective case–control study of consecutive specimen comprising 32 serous carcinomas and 31 controls (10 normal adnexa, 10 benign and 6 atypically proliferative surface epithelial tumors, and 5 other carcinomas). Subjects and Methods: Sectioning and extensive examination of the fimbrial end (SEE‑FIM) protocol along with immunohistochemistry for Bcl‑2, p53, and Ki‑67 was employed for evaluating invasive carcinoma and precursor lesions in cases versus controls. Results: SCOUT, p53 signatures, and STIC were most frequent in the serous carcinomas. p53 signatures and STIC were always seen in the fimbrial end. STICs were exclusively present in serous carcinomas, more common in ipsilateral tubes of cases with dominant ovarian mass. Multifocal p53 signatures with STIC were seen in 7 (21.9%) cases. STIC was present with or without an invasive carcinoma in 25% and in 6.25% of cases of pelvic serous carcinomas, respectively. The junctional epithelia did not show any lesion in any group. Conclusions: SEE‑FIM protocol is recommended for evaluation of sporadicpelvic (ovarian/tubal/peritoneal) serous carcinoma. Based on the presence of STIC or invasive carcinoma, nearly 60% of all pelvic serous carcinomas are of fallopian tubal origin.

Liquid-based cytology versus conventional cytology for evaluation of cervical Pap smears: Experience from the first 1000 split samples.

Context and Aim: Screening programs using conventional cytology conventional Pap smear (CPS) have successfully reduced cervical cancer, but newer tests like liquid-based cytology (LBC) and human papillomavirus testing might enhance screening. The main aim of the present study was to assess the diagnostic accuracy of LBC versus CPS using “split samples.” Materials and Methods: This was a prospective study comprising of 1000 consecutive cervical “split samples” over a period of 1 year. Split sample was obtained using cervex-brush. CPS was prepared from the brush and the brush head was suspended in the LBC vial and processed by SurePath™ LBC. Results: There were 4.3% unsatisfactory (U/S) cases in CPS and 1.7% in LBC; the main cause is insuffi cient cells, and excess of blood in CPS. About 25/100 (2.5%) split samples had epithelial abnormalities both in CPS and LBC (1.2%-atypical squamous cells of undetermined signifi cance; 0.4%-low grade squamous intraepithelial lesion; 0.2%-high grade squamous intraepithelial lesion; 0.5%-squamous cell carcinoma; 0.1%-atypical glandular cells favouring neoplasia; 0.2%-adenocarcinoma). Infl ammatory organisms were almost equally identifi ed in both techniques but were better seen in LBC samples. Conclusions: LBC technique leads to signifi cant reduction of U/S rate. LBC samples offered better clarity, uniform spread of smears, less time for screening and better handling of hemorrhagic and infl ammatory samples. LBC had equivalent sensitivity and specifi city to CPS.

Female adnexal tumor of probable Wolffian origin.

Female adnexal tumor of probable Wolffi an origin (FATWO) is a rare neoplasm arising from the remnants of the mesonephric duct. We report here a case of FATWO in a 70-year-old woman arising from the broad ligament and confi rmed on immunohistochemistry. Most of these tumors behave in a benign fashion but certain histological features like hypercellularity, cellular pleomorphism and nuclear atypia as seen in the index case may increase the rate of recurrence and metastasis. Therefore, close follow-up is recommended for FATWO.

Protein p 16INK4A expression in cervical intraepithelial neoplasia and invasive squamous cell carcinoma of uterine cervix.

The association of human papilloma virus (HPV) infection and cervical intraepithelial neoplasia (CIN) is well recognized. Interaction of HPV oncogenic proteins with cellular regulatory proteins leads to up regulation of p16 INK4A , a CDK inhibitor, which is a biomarker for HPV infection. We investigated p16 expression in CIN and invasive squamous cell carcinoma (SCC) which has not been reported in the Indian population previously. Materials and Methods: Retrospective analysis of 100 cases with 20 cases each of histologically normal cervical epithelium, CIN1, 2, 3 and invasive SCC for p16 expression was performed by immunohistochemistry using commercially available mouse monoclonal antibody to p16 (clone 6H12). Statistical Analysis: For differences in expression among groups, statistical analysis was carried out using ANOVA and post hoc test of Scheffe. Results: p16 immunoreactivity was found to be both nuclear and/or cytoplasmic. The normal cervical epithelium was predominantly negative for p16 (18/20). There was a progressive increase of p16 expression with the grade of CIN. In CIN 1, two cases (20%) showed nuclear and nucleocytoplasmic positivity respectively. In contrast, diffuse strong nuclear or nucleocytoplasmic expression was observed in 45 and 55% cases of CIN 2 and CIN 3 respectively. All except one squamous cell carcinoma stained strongly positive for p16. The difference in expression between CIN 2/3 and SCC versus normal cervix was found highly significant (p is equal to 0.008 and p less than 0.001). Conclusions: p16 expression correlates excellently with the grade of CIN and is a sensitive marker of cervical intraepithelial neoplasia.

Cytology of Hürthle cell neoplasms of thyroid gland.

Hürthle cell neoplasms (HCN) are an uncommon group of tumors of the thyroid gland. Fine needle aspiration cytology (FNAC) is an important diagnostic tool in solitary nodules of the thyroid gland. A 5-year retrospective analysis of all cases diagnosed as HCN on cytology was performed and correlated with the corresponding histopathology wherever available. There were 13 cases diagnosed as HCN out of which 6 cases had subsequent histopathologic examination. Four were adenomas and two were carcinomas. In addition, 3 cases that were adenomas on histopathology were reported on cytology as colloid goiter with cystic degeneration in 2 cases and as follicular adenoma in 1 case. There was extensive cystic degeneration in the former two cases whereas poor cellular preservation led to misdiagnosis in the third case. There were no specific cytomorphological features that distinguished adenoma from carcinoma. FNAC has a high specificity for a diagnosis of HCN, but the sensitivity is not as high because of sampling error.

Does c-erbB-2 expression have a role in medulloblastoma prognosis?

The prognosis of patients with medulloblastoma has remained same for the last two decades. This study evaluated the role of c-erbB-2 expression in medulloblastoma as a prognostic marker. Fifty cases of medulloblastomas were investigated for the expression of c-erbB-2 protein using immunohistochemistry. The expression of c-erbB-2 was correlated with age, histology and disease-free survival (DFS). Thirty-five (70%) tumors were c-erbB-2 positive. Immunoreactivity for c-erbB-2 receptor was observed as mixed cytoplasmic and membrane positivity of tumour cells. The mean DFS in c-erbB-2 positive cases was 19.81 months compared to 48.33 months in c-erbB-2 negative cases. c-erbB-2 positivity was found to be an independent predictor of poor outcome in medulloblastoma (p value < 0.05). No correlation of c-erbB-2 expression was observed with the age of patient and the histological type of tumour. Additionally, c-erbB-4 expression was also evaluated in these tumours. Thirty-three cases showed co-expression of c-erbB-2 and c-erbB-4 proteins. However, c-erbB-4 expression alone was not associated with poor outcome, whereas its co-expression with c-erbB-2 was associated with shorter DFS (p < 0.05).

Recurrent endocervical-like mucinous borderline tumor (ELMBT) arising in a case of long-standing endometriosis--a case report.

Endometriosis is a well-known precursor lesion of ovarian malignancies, particularly those of endometrioid and clear-cell types and rarely of serous or mucinous types. The association of endometriosis with mucinous borderline tumors also varies. This case is of a 60 year old female, who had a long history of more than thirty years of endometriosis and developed recurrent endocervical-like mucinous borderline tumor (ELMBT) in endometriotic foci. This case highlights challenges in the management of such complications associated with endometriosis and emphasizes the importance of long-term follow-up in cases of endometriosis.

Spermatic granuloma presenting as an epididymal nodule: fine needle aspiration cytological findings and differential diagnosis.

Spermatic granuloma is a granulomatous lesion that presents clinically as a nodular lesion in the region of epididymis. There are only few documented cases of spermatic granuloma in the literature. Fine needle aspiration (FNA) reveals mixed inflammatory cells comprising of plenty of macrophages along with lymphocytes and scattered polymorphs in a fluidy background containing many spermatozoa and sperm heads. Sperm heads are also noted within macrophages. Ill formed to well-formed granulomas were seen in all the cases. FNA has an important role in the differential diagnosis of epididymal nodule as it can rule out malignancy and other benign cytological diagnosis like tuberculosis, acute and chronic epididymo-orchitis. Distinction of spermatic granulomas from the more common tuberculous granulomatous infection is important from the cytopathologist's point of view. By providing an accurate and rapid diagnosis, FNA prevents aggressive and potentially inappropriate surgical procedures.