Expression of HER2 and EGFR Proteins in Advanced Stage High-grade Serous Ovarian Tumors Show Mutual Exclusivity.

Human epidermal growth factors play an important role in ovarian carcinogenesis and are evaluated for prognostic and possible therapeutic roles in high-grade serous ovarian malignancies. The present study was undertaken to evaluate the expression of human epidermal growth factor receptor 2 (HER2) and epidermal growth factor receptor (EGFR) in advanced stage serous carcinoma and their influence on prognosis. The expression of HER2 and EGFR was studied in 59 cases of stage III and IV ovarian serous carcinomas by immunohistochemistry and fluorescent in situ hybridization. Of the 48 interpretable tumors for HER2, 6 tumors (12.5%) were scored as positive, 14 (29%) as equivocal and 28 tumors (58.5%) were negative by immunohistochemistry, while only 2/48 (4%) showed frank amplification by fluorescent in situ hybridization with ≥4 copies per cell. HER2 gene expression measured by quantitative polymerase chain reaction had good positive correlation with both protein expression and gene amplification. Although EGFR expression was seen in 32% of tumors, none of the tumors positive for HER2 protein or gene amplification had co-expression of EGFR indicating mutual exclusivity of their expression. Gene expression of both proteins also confirmed their inverse correlation (Pearsons CC=-0.15, P=0.3). Further there was no influence of protein or gene expression of these markers on the overall survival. In conclusion, HER2 and EGFR are expressed in a small percentage of tumors and the mutual exclusivity of these markers precludes the possibility of dual targeting with anti-HER2 and anti-EGFR therapy in advanced stage high-grade serous ovarian carcinoma.

Maintenance of pegylated liposomal doxorubicin/carboplatin in patients with advanced ovarian cancer: randomized study of an Asian Gynecologic Oncology Group.

OBJECTIVES: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. METHODS: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m², n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. RESULTS: Enrollment was slow, accrual was closed when 7+ years had passed. With a median follow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19-0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCA/non-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11-1.18; p=0.091). CONCLUSIONS: Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

Decreased Survival With Mastectomy Vis-à-Vis Breast-Conserving Surgery in Stage II and III Breast Cancers: A Comparative Treatment Effectiveness Study.

PURPOSE: The primary purpose of hospital-based cancer registries is assessing patient care. Clinical stage-based survival and treatment-based survival are some of the key parameters for such assessment. Because of the challenges in obtaining follow-up parameters, a separate study on patterns of care and survival was undertaken by the Indian National Cancer Registry Program. The results for cancer of the female breast are presented here. PATIENTS AND METHODS: Data abstracted in a standardized patient information form were transmitted online to a central repository. Treatment patterns were assessed for 9,903 patients diagnosed between January 1, 2006, and December 31, 2008, from 13 institutions. Survival analysis was restricted to 7,609 patients from nine institutions wherein follow-up details (as of December 31, 2012) were available for at least 60% of patients. RESULTS: The overall 5-year survival rates with breast-conserving surgery (BCS) and mastectomy (MS) were 94.0% and 85.8%, respectively, for stage II disease (adjusted hazard ratio, 2.40; 95% CI, 1.8 to 3.2) and 87.1% and 69.0%, respectively, for stage III disease (hazard ratio, 2.82; 95% CI, 2.2 to 3.7). Patients who had MS did better with systemic therapy (chemotherapy and/or hormone therapy), whereas patients with BCS required just local radiation therapy to achieve best survival. CONCLUSION: This observational study in the natural setting of care of patients with cancer in India showed significantly decreased survival with MS when compared with BCS. The reasons for lower survival with MS and the biologic or scientific rationale of the necessity of systemic therapy to achieve optimal survival in patients undergoing MS but not in those with BCS need further investigation.

Intra and Inter-Observer Variability of Transformation Zone Assessment in Colposcopy: A Qualitative and Quantitative Study.

INTRODUCTION: Colposcopy is an important tool in the diagnosis of cervical precancer and early cancer. The assessment of women with abnormal cytology and selection of those who require further therapy or follow up depends on the colposcopic assessment of the Transformation Zone (TZ). Identification of the TZ is thus an important part of this examination. Intra and inter-observer variability is known to be relatively high in the colposcopic interpretation of abnormal features. However, there are hardly any studies on the observer variability in the assessment of the type of TZ. AIM: The present study was conducted with the aim to compare the intra and inter-observer variability of the TZ type classification and the Squamo-Columnar Junction (SCJ) visibility and to quantitatively measure the intra and inter-observer correlations of tracing of the TZ contours. MATERIALS AND METHODS: Colposcopy images were obtained for a total of 170 cases. They were reviewed by three colposcopists independently. The colposcopists classified the TZ type and also marked the SCJ contours on the images. Each observer independently reviewed the cases on two different instances (few weeks apart) and the result was compiled for intra-observer variation. The intra and inter observer variability on the TZ type was compared using Cohen's Kappa. This was followed by a quantitative measurement of TZ observation variability using Hausdorff distance. RESULTS: The inter-observer agreement for the TZ type classification was moderate (Kappa= 0.53 to 0.66). The Intra-observer agreement was moderate to strong (0.60 to 0.86). CONCLUSION: Colposcopic in vivo examination increases the variability in the identification of the TZ when compared to the analysis of recorded images. The disagreement in the TZ type was mostly in categories Type 2 vs Type 3 followed by Type 1 vs Type 2. A computerized quantification method can be used for quality control and training purpose in colposcopy.

"The Jelly Belly": Diagnostic Dilemmas and Current Concepts.

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare and poorly understood clinicopathological entity characterized by gelatinous ascites with neoplastic or non-neoplastic mucinous implants in the peritoneum. Although its origin was debated, current evidence in literature favours the appendix as the origin of the disease, over the ovaries. The changing terminologies in the classification of this entity pose diagnostic and management challenges. CASE REPORTS: Herein, we report three cases of PMP in postmenopausal women, their clinical presentation, pathological staging based on the peritoneal tumor deposits and the treatment administered. Two patients recovered uneventfully, while one had recurrence of adenocarcinoma. CONCLUSION: The rarity of this disease and the diagnostic challenges associated with it are discussed with an emphasis on the current concepts in its origin and management. Appropriate classification and complete removal of the tumor is mandated to prevent disease-related mortality.

Concurrent Chemoradiation for Cancer of the Cervix: Results of a Multi-Institutional Study From the Setting of a Developing Country (India).

PURPOSE: The primary output of hospital-based cancer registries is data on cancer stage and treatment-based survival that can be used to evaluate patient care, but because there are many challenges in obtaining follow-up details, a separate study on patterns of care and patterns of survival for patients at selected sites was initiated under the National Cancer Registry Programme of India. This article presents the results for cervical cancer. PATIENTS AND METHODS: A standardized patient information form was used to record patient information, and data were entered into a central repository-the National Centre for Disease Informatics and Research. The study patients were from 12 institutions and were diagnosed between January 1, 2006, and December 31, 2008. Patterns of treatment were assessed for 7,336 patients, and patterns of survival were determined for 2,669 patients from six institutions, at least 70% of whom had data regarding follow-up as of December 31, 2012. RESULTS: Of 7,336 patients, 55.5% received optimal radiotherapy (RT). In all, 80.9% of patients had locally advanced cancers (stage IIB to IVA), 51.1% received RT alone, and 44.4% received concurrent chemoradiation (RTCT). In 1,753 patients with locally advanced cancers, significantly better survival was observed with RTCT than with RT alone (5-year cumulative survival, 70.2% v 47.3%; hazard ratio, 0.48; 95% CI, 0.41 to 0.56). CONCLUSION: A conservative estimate indicates that, on an annual basis, 38,771 patients with cervical cancers in India alone do not get the benefit of RTCT and thus they have poorer survival. There is a need to reiterate the National Cancer Institute's alert that advised supplementing chemotherapy to radiation for locally advanced cancer of the cervix in the context of the developing world, where 84.3% of cancers of the cervix occur.

A study of pelvic and para-aortic lymph node involvement in surgically staged endometrioid carcinoma of endometrium.

PURPOSE: The purpose of this study was to investigate the influence of the depth of myometrial invasion and tumor grade on lymph node involvement in endometrial carcinoma. METHODS: Patients with endometrioid carcinoma of endometrium who underwent surgical staging between January 1999 and September 2010 under the division of gynecologic oncology were studied retrospectively. Patients treated by radiotherapy or chemotherapy before surgeries were excluded. RESULTS: The study group included 61 patients. Six patients had lymph node metastasis, of which 83.3 % had >50 % myometrial invasion (P = 0.052). Grades 1, 2, and 3 were each seen in 33.3 % of them (P = 0.061). When the study group was divided into two sets, namely, those with <50 and >50 % myometrial invasion, the odds ratio was 10.3, which means that the chance of the prevalence of lymph node metastasis in the latter group is 10 times more. CONCLUSIONS: Although the P value was not significant, the odds ratio reveals that there is an increased risk of lymph node positivity with deeper myometrial invasion. Surgical staging needs to be done for all operable cases of carcinoma endometrium to determine the prognosis and further management.

Ovarian serous carcinoma: relationship of p53 and bcl-2 with tumor angiogenesis and VEGF expression.

The aim of the study was to assess the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression in ovarian serous carcinoma and to examine their relation with apoptosis.Paraffin-embedded specimens of 41 cases of ovarian serous carcinomas were evaluated by immunohistochemistry for VEGF, p53, and bcl-2 expression. MVD was assessed with CD31 staining. We investigated the association of tumor angiogenesis (MVD and VEGF) with clinicopathologic factors, p53 overexpression, and bcl-2 expression.There was a significant correlation between high MVD and suboptimal debulking and advanced stage disease. A significant negative correlation was expressed between bcl-2 and VEGF expression. In univariate analysis, only stage had a significant impact on disease-free survival.The results of this study suggest that higher degree of angiogenesis is associated with suboptimal debulking and advanced-stage disease. Expression of VEGF had negative association with VEGF expression.

Significance of preoperative thrombocytosis in epithelial ovarian cancer.

BACKGROUND: Reactive thrombocytosis is reported in a variety of solid tumors. A few studies have documented preoperative thrombocytosis in ovarian cancer and identified it as a marker of aggressive tumor biology. AIM: To study the incidence of preoperative thrombocytosis (platelets greater than 400x10) in epithelial ovarian cancer and its association with other clinicopathologic factors. MATERIALS AND METHODS: Sixty-five patients with invasive ovarian epithelial cancer were retrospectively reviewed and analyzed for the association preoperative thrombocytosis with other clinical and histopathological prognostic factors. Means were analyzed by Student's t test; proportions were determined by Chi-square analysis. RESULTS: Twenty of 65 (37.5%) patients had thrombocytosis at primary diagnosis. Patients with preoperative thrombocytosis were found to have lower hemoglobin (P < 0.0002), more advanced stage disease (P < 0.05) and higher grade tumors (P < 0.02). Patients with thrombocytosis had greater likelihood of subpotimal cytoreduction. CONCLUSIONS: Preoperative thrombocytosis is a frequent finding in ovarian carcinomas and their association with advanced stage disease and higher grade denotes that platelets play a role in the tumor growth and progression.

Ovarian lymphoma.

The involvement of the ovary in lymphomatous processes is rare. Such an involvement can occur in 2 ways, either primary or secondary, which usually presents with abdominal or pelvic complaints. We present a case of secondary involvement of the ovary with occult extra-ovarian nodal disease and discuss the histogenesis of ovarian lymphomas with criteria for diagnosis and differential diagnosis.