BRCA1 promoter methylation & its immunohistochemical correlation in sporadic breast cancer

Background & objectives: Studies have shown that apart from hereditary breast carcinomas, breast cancer susceptibility gene 1 (BRCA1) mutations conferring to its loss are seen in sporadic breast carcinomas (SBC) as well. The aim of the present study was to assess BRCA1 methylation in females presenting at King George’s Medical University, Lucknow, with SBC by both immunohistochemistry (IHC) and methylation PCR with respect to hormonal profile and various morphological prognostic parameters. The primary objective was to look for the association between BRCA1 protein expression and DNA promoter methylation. Methods: 81 mastectomy specimens from SBC of invasive breast carcinoma (no special type) were included in this study. After a detailed morphological assessment, formalin fixed paraffin embedded tissue from a representative tumour area was selected for BRCA1 IHC by heat-mediated antigen retrieval under high pH and DNA extraction and further bisulphate treatment. BRCA1 was studied for methylation by methylated and unmethylated PCR-specific primers. Results: BRCA1 promoter methylation was present in 42/81 (51.9%) participants, with significant BRCA1 protein loss (72.7%; P=0.002). A significant association between BRCA1 loss and hormonal profile was found (P=0.001); maximum in triple negative breast carcinoma (TNBC) (72%; 18/25). Most of the TNBC also harboured methylation (68%). Although not significant grade II and III tumours, lymph vascular invasion, ductal carcinoma in situ, and nodal metastasis (?3) were seen in a higher percentage in methylated tumours. Mortality in SBC was significantly associated with BRCA1 loss (30.3%; P=0.024). Interpretation & conclusions: Study results highlight the concept of “BRCAness” in SBC as well. Hence, we can confer that identification of BRCA1 loss in SBC can make it a perfect candidate for poly ADP- ribose polymerase inhibitors or cisplatin-based therapy like hereditary ones.

Synchronous occurrence of lobular breast carcinoma and granulosa cell tumor of ovary mimicking metastatic lobular breast carcinoma

Breast cancer is one of the main sources of ovarian metastasis. Diffuse sheet of lobular carcinoma cells can strongly mimic granulosa cell tumor (GCT) which itself is a rare ovarian neoplasm constituting <5% of all the ovarian neoplasms. A 55-year-old female presented with a painful lump in the right breast associated with nipple discharge for 4 months, which on radiological and cytological findings was suspicious of an epithelial malignancy. During routine work-up, a solid-cystic lesion in the left ovarian adnexa was identified. The patient underwent right modified radical mastectomy along with left salpingo-oophorectomy. Histopathological and immunohistochemical features confirmed the diagnosis of a synchronous lobular carcinoma breast with GCT ovary. Simultaneous occurrence of Lobular carcinoma breast (LCB) and GCT ovary is extremely rare. Morphologically, these can look similar, raising a suspicion of LCB metastasis to ovary. This is important to differentiate the two for a proper patient management and prognosis

Role of serum HE4 as a prognostic marker in carcinoma of the ovary

BACKGROUND: Epithelial ovarian cancer is the second most common gynecological cancer. Human Epididymis Protein 4 is a novel biomarker for ovarian cancer. This study aims to explore the role of HE4 in monitoring recurrence and prognostication of ovarian cancer by predicting overall survival (OS) and progression-free survival (PFS). MATERIALS AND METHODS: In total, 149 patients with ovarian carcinoma were enrolled in the study. Baseline and post-treatment 3 monthly biomarker levels were recorded. For analysis, patients were divided into primary debulking surgery (PDS) and interval debulking surgery (IDS) groups. Statistical analysis was done using SPSS 24. RESULTS: Median age of patients at diagnosis was 45 (19–75) years. Recurrence was seen in 68.5% (n = 102) patients. The sensitivity of serum HE4 in detecting recurrence was 85.3% (95%CI: 76.95%–91.5%) and specificity was 91.5% (95%CI: 89.5%–98.2%). A >80% decline in HE4 levels during treatment indicated a better PFS, which was statistically significant in both groups (P = 0.04 in PDS and P = <0.001 in IDS group). Multivariate analysis suggested that OS was influenced by optimal cytoreduction in both groups of patients and stage in the IDS group. On the contrary, PFS was influenced by stage and response in HE4 levels in both groups. CONCLUSION: HE4 levels have similar sensitivity but more specificity when compared with CA125 in diagnosing recurrent ovarian cancer. A >80% decline in HE4 levels during treatment predicts better PFS and can help in prognostication

Biomarkers towards Ovarian Cancer Diagnostics: Present and Future Prospects

ABSTRACT Ovarian carcinoma accounts for highest mortality of all gynecologic malignancies as the disease is asymptomatic until late stages. Biomarkers such as CA-125 and HE4 are being currently used for diagnosis of ovarian cancer, but they show contradicting diagnostic accuracy. Therefore other biomarkers have been investigated for early detection of this disease, but no success has been obtained and no test has yet been recommended for screening a general population. In this instance, aptamers can be effectively used to identify tumor-specific antigens for early diagnosis and targeted therapy of ovarian cancer. This article provides an overview of the biomarkers/panels being explored as well as the potential of aptamers to improve current long-term survival rates of ovarian cancer.

Giant fibrosarcoma of anterior abdominal wall: a rare case report and review literature.

Adult type fibrosarcoma is very rare malignant soft tissue tumor. It usually arises in soft tissues of extremities, trunk, head and neck. Fibrosarcoma is essentially a diagnosis of exclusion from other spindle cell mesenchymal malignant neoplasm; by definition negative for epithelial, myogenous and neural markers on immunohistochemistry. To the best of our knowledge, very few cases have been reported in the literature. We here report a case of giant fibrosarcoma arising from anterior abdominal wall in a recurrent dermatofibrosarcoma proturbens and managed with surgical excision and reconstruction with meshplasty.

In vitro evaluation of cytotoxicity of denture adhesives.

Aim: The aim of the study is to assess and compare the cytotoxicity of commercially available four denture adhesives ex-vivo. Materials and Methods: Four commercially available denture adhesives namely Metrodent powder, Fixon powder, Dentiro powder and Fixon cream were selected. Normal saline was used in control group. To evaluate the cytotoxicity of denture adhesives, macrophages were isolated from peritoneal cavity of Swiss albino mice and cell integrity/cell viability method was done by using trypan blue dye. Results: Viable cells were counted and subjected to statistical analysis. ANOVA, F and 't' test were performed, which showed statistically significant values (P < 0.001). The mean percentage of viable cells was highest in the control group (95%) and lowest in Fixon powder (55.66%), with Dentiro powder the mean percentage of viable cells was 63.66%, with Metrodent powder 67.6% while with Fixon cream it was 69.33%. Conclusion: All tested denture adhesives showed varied degree of cytotoxicity that is statistically significant. The degree of toxicity was more in Fixon powder followed by Dentiro powder and Metrodent powder with least in Fixon cream.

Juvenile nasopharyngeal angiofibroma: a single institution study.

BACKGROUND: Juvenile nasopharyngeal angiofibroma (JNA) is a rare tumor of adolescent males and there is a paucity of Indian studies on this subject. AIMS: To present the experience of management of JNA at a single institution. SETTING AND DESIGN: This is a retrospective observational study of patients with JNA who presented at the Tata Memorial Hospital between May 1988 and August 2001. MATERIALS AND METHODS: Thirty-two patients with JNA were treated in the study period. Since the time period was prolonged and diagnostic and therapeutic protocols had undergone many changes, the patients were divided into two groups, namely 1988-1996 and 1997-2001. The age distribution, disease patterns, management approaches and treatment outcomes of patients in the two groups were recorded. Statistical analyses were done using students 't' test and test for proportion. RESULTS: The mean age at presentation was 16 years and more than 90% of the patients had Stage III or IV disease. Preoperative embolization was carried out in 19 patients. The surgical approaches used were median maxillectomy, infratemporal fossa, transpalatal, maxillary swing and craniofacial approach. The recurrence rate, complete resection rate and cure rates were 12.5%, 41% and 63% respectively. CONCLUSION: Surgery is the mainstay of treatment of JNA. Preoperative embolization and newer surgical approaches result in less blood loss and complete resection. Aggressive re-resection should be done for resectable recurrences reserving radiotherapy for unresectable, recurrent/ residual disease.