Cherry Bansal

Common genetic variants in pre-microRNAs and risk of breast cancer in the North Indian population

Objective MicroRNAs (miRNAs) are short regulatory RNAs that can modulate gene expression and function as negative regulators. Common genetic variants like single nucleotide polymorphisms (SNPs) in miRNA genes may alter their expression or maturation resulting in varied functional consequences in carcinogenesis. Therefore, we evaluated the genetic variants in pre-miRNAs: hsa-miR-146a G/C (rs2910164), hsa-miR-196a2 C/T (rs11614913), and hsa-miR-499 T>C (rs3746444) for their role in breast cancer susceptibility. Study design The study comprised 121 breast cancer patients, 115 with benign breast disease, and 164 controls. The genotypic frequency of miRNA polymorphisms was determined by PCR-RFLP assay. Logistic regression was used for statistical analysis using SPSS Software version 15.0. In silico analysis was done using various bioinformatics tools (F-SNP, FAST-SNP). Results The heterozygous variant of miR-146a G/C (rs2910164) is associated with the reduced risk of breast cancer at the genotype level as well as at the allele level (p < 0.05, OR = 0.5) as compared to controls. On the contrary, no significant difference was observed in the distribution of miR-196a2 C/T (rs11614913) and miR-499 T>C (rs3746444) polymorphisms in any groups both at genotype and allele levels. On the other hand, in multivariate analysis, we found that the miR-196a2 (rs11614913) C>T was associated with an increased risk of breast cancer risk in postmenopausal females (p = 0.02, OR = 3.2). We also attempted to find out the risk of malignant breast disease in relation to each of the above SNPs on dividing our data on the basis of benign and malignant status, but no significant difference was observed. In silico analysis using F-SNP showed change in transcriptional regulation by miR-146a G/C (rs2910164), miR-196a2 C/T (rs11614913) and miR-499 T>C (rs3746444) variations; the functional score was 0.100, 0.065 and 0.277, respectively. Conclusion The results of the present study demonstrate that miR-146a G/C (rs2910164) polymorphism is associated with reduced genetic susceptibility to breast cancer. However, multivariate analysis showed as miR-196a2 (rs11614913) C>T to be associated with increased risk of breast cancer risk in postmenopausal females. Further multicentric studies involving a large number of cases need to be carried out to strengthen the present results.

Comparative evaluation of the modified Scarff-Bloom-Richardson grading system on breast carcinoma aspirates and histopathology

Background: Fine needle aspiration (FNA) is a quick, minimally invasive procedure for evaluation of breast tumors. The Scarff-Bloom-Richardson (SBR) grade on histological sections is a well-established tool to guide selection of adjuvant systemic therapy. Grade evaluation is possible on cytology smears to avoid and minimize the morbidity associated with overtreatment of lower grade tumors. Aim: The aim was to test the hypothesis whether breast FNA from the peripheral portion of the lesion is representative of Scarff-Bloom-Richardson grade on histopathology as compared to FNA from the central portion. Materials and Methods: Fine-needle aspirates and subsequent tissue specimens from 45 women with ductal carcinoma (not otherwise specified) were studied. FNAs were performed under ultrasound guidance from the central as well as the peripheral third of the lesion for each case avoiding areas of necrosis/calcification. The SBR grading was compared on alcohol fixed aspirates and tissue sections for each case. Results: Comparative analysis of SBR grade on aspirates from the peripheral portion and histopathology by the Pearson chi-square test (χ2 =78.00) showed that it was statistically significant (P<0.001) with 93% concordance. Lower mitotic score on aspirates from the peripheral portion was observed in only 4 out of 45 (9%) cases. The results of the Pearson chi-square test (χ2 = 75.824) with statistically significant (P=0.000). Conclusion: This prospective study shows that FNA smears from the peripheral portion of the lesion are representative of the grading performed on the corresponding histopathological sections. It is possible to score and grade by SBR system on FNA smears.

Literature meta-analysis of zosteriform cutaneous metastases from melanoma and a clinico-histopathological report from India

Cutaneous metastases in patients with malignant tumours are an important clue to tumour progression or even the first manifestation of malignancy. Among the various topographic patterns of cutaneous metastasis, the zosteriform pattern of metastasis is rare, and very few cases have been published. Various theories have been proposed for this zosteriform pattern of metastases, but none have been proved. We collected the available PubMed articles on zosteriform skin metastasis from cutaneous melanoma published since 1970 and reviewed the cases, including our own case. Melanoma presents with cutaneous metastasis in up to 44% of patients. Clinicians treating oncology patients should consider zosteriform skin metastasis in the differential diagnosis of zosteriform lesions to avoid inadequate diagnosis and management.

Solitary cylindroma with malignant transformation.

A 59-year-old woman presented with a history of rapidly progressive recurrent tumor of 6.5 cm diameter of the scalp. Histopathological examination revealed a case of malignant cylindroma. There has been no recurrence or metastases and the patient is disease free at the end of 15 months postoperatively. Malignant transformation occurs less often in solitary form of cylindroma, but once transformed, tumors behave aggressively with extensive local infiltrative growth or metastases. The case is reported to document a rare case of malignant cylindroma arising in a patient with solitary cylindroma on the parieto-temporal region.

Correlation of hormone receptor and human epidermal growth factor Receptor-2/neu expression in breast cancer with various clinicopathologic factors

Background: A significant development in the breast carcinoma management is the correlation between the presence of hormone receptors in the tumor and response to hormonal therapy and chemotherapy. Human epidermal growth factor receptor-2/neu (Her-2/neu) overexpression also serves as a very useful parameter to predict response to herceptin. Aim of Study: The study was conducted to correlate immunohistochemical expression of markers such as estrogen receptor (ER), progesterone receptor (PR), and Her-2/neu with various clinicopathologic parameters. Materials and Methods: The study included 509 cases of breast carcinoma over a period of 5 years (from May 2009 to May 2014). Immunohistochemistry (IHC) for ER, PR, and her-2/neu was performed. Results: ER positivity was observed in 42.8% (218/509) cases, PR positivity in 31.8% (194/509) cases whereas her-2 neu positivity was seen in 40.7% (203/509) cases. Triple marker (ER, PR, and Her-2/neu) negative cases were 23.6% (120/509) cases. ER and PR expression was found to have a statistically significant correlation with tumor grade. Statistically significant correlation was observed between tumor size and tumor grade and her-2/neu expression. Her-2/neu expression showed statistically significant association with tumor stage. As the tumor grade increased, the proportion of triple-negative cases went on increasing, which was statistically significant. Conclusion: IHC has an increasingly important prognostic role in determination of factors that affect clinicopathologic features. Nevertheless, the results of this large series showed different patterns of findings with respect to clinicopathologic features.

Circulating Tumor Cells in Breast Cancer: Correlation with Clinicopathological Parameters, Hormone Profile and MicroRNA Polymorphisms.

Abstract Objective: Circulating tumor cells are isolated tumor cells in the peripheral blood that serve as important prognostic indicators for many kind of tumors. The study was conducted to know the rate of detection of circulating tumor cells among breast cancer patients in comparison with benign breast diseases and control subjects and to know the association between CTC positivity and various clinicopathological parameters, hormonal profile and microRNA polymorphisms. Material and Method: In the present case control study, we included 182 healthy controls, 108 cases of benign breast disease and 114 breast carcinoma cases. Various clinicopathological details of cases were recorded. Immunohistochemistry was performed for estrogen (ER) and progesterone receptors (PR) and Her-2 neu. Circulating tumor cells were analyzed using flow cytometry (EpCAM, CK, CD45). Genotypic frequency of micro RNA polymorphisms was determined by PCR-RFLP assay. Results: Circulating tumor cell positivity was observed in 11/114 (9.64%) breast cancer cases but absent in benign and control groups, and was significantly associated with tumor size, histologic type, tumor grade, metastasis and skin infiltration (p<0.05). Circulating tumor cell positivity did not show any correlation with the immunohistochemical profile. No significant associations between pre-miRNA genetic variations miR-196a2 C/T (rs11614913), miR-146a G/C (rs2910164) and miR-499 T>C (rs3746444) polymorphisms and circulating tumor cell positivity were observed. Conclusion: The flow cytometry protocol for detection and molecular characterization of circulating tumor cells is a time and cost-effective technique, suitable for routine clinical use. However, more elaborate studies are needed to establish the findings as our study was limited by small sample size.

Erythrodermic mycosis fungoides with hypereosinophilic syndrome: a rare presentation

Mycosis fungoides (MF) is the most common variant of primary cutaneous T-cell lymphoma (CTCL). It is generally associated with an indolent clinical course and characterised by well-defined clinicopathological features. Although rare, CTCLs constitute 65% of all cutaneous lymphoid malignancies, of which 50% are patients with MF. The erythrodermic variants of MF, a malignancy of mature, skin homing and clonal T lymphocytes, usually present in mid to late adulthood. Association with hypereosinophilia is important in prognosis. We report a case of erythrodermic MF with hypereosinophilic syndrome in a 22-year-old female presenting with gradually progressive intractable erythroderma with intensely pruritic multiple papules, plaques, and nodules involving more than 90% of body surface area. Diagnosis was confirmed by histopathological examination and immunophenotyping from multiple skin biopsies.

Role of fine needle aspiration cytology in diagnosing filarial arm cysts

Filariasis is prevalent in tropical and subtropical areas and is endemic in regions of India. Lymphatic filariasis in India is caused mainly by two species of nematodes: Wuchereria bancrofti and Brugia malayi, which invade the human lymphatic system. We report two cases of superficial cystic lesions of the upper limb revealed on fine needle aspiration (FNA) to be clinically unsuspected filariasis. Despite similar aetiologies, both cases revealed variations in aspirate nature, smear morphology and peripheral blood findings. FNA provides definitive diagnosis and is an important tool for diagnosing soft tissue swellings owing to filariasis.