Comparative Study of DNA ploidy and BRAF Immunohistochemistry between Colonic Adenocarcinoma and Inflammatory Colonic Lesions.

OBJECTIVES: To evaluate DNA ploidy and S-phase fraction (SPF) in non-Lynch colonic adenocarcinoma, ulcerative colitis (UC), Crohn disease (CD) which are known as risk factors, and colitis. We correlated ploidy and SPF with tumor grading, staging and BRAF expression. METHODS: All studied adenocarcinomas have intact mismatch repair genes as proved by immunohistochemistry. All were assessed for ploidy by automated image-based DNA cytometry and histograms were drawn. Immunostaining by anti-BRAF V600E was performed. Diagnostic laparoscopy (DL) was done as a preliminary step for staging GI cancers. RESULTS: there is significant difference in DNA ploidy between groups; 77.5% and 17.5% of aneuploid cases are adenocarcinoma and UC. Groups are compared in terms of 2C, 4C, above 4C DNA content and SPF and significant difference is principally found between adenocarcinoma group and others. In adenocarcinomas, DNA ploidy is significantly correlated with tumor staging and grading. Regarding BRAF expression, there is significant difference between groups; all adenocarcinomas, 83.33% of UC were positive, while all cases of colitis, bilharzial colitis, CD were negative. There is significant relation between BRAF and SPF among all diploid cases including adenocarcinoma, and among non-neoplastic diploid cases. There is direct significant relation between BRAF intensity and adenocarcinoma staging. There is no significant difference between BRAF and ploidy among UC cases, although 75% of aneuploid UC are positive. DL helps in GI cancer staging. Routine laparoscopy before laparotomy, especially in cancers which have equivocal operability helps to avoid unnecessary laparotomies. CONCLUSION: Based on significant difference in ploidy between adenocarcinoma and UC and between SPF and ploidy, assessment of ploidy by DNA cytometry for UC and other colitis could therefore predict impending malignant transformation before development of colonic dysplasia. Also measuring SPF in adenocarcinoma helps to select patients who could greatly benefit from chemotherapy. DL has vital role in staging GI cancers.

Durable Response of Androgen Receptor-Positive Male Breast Cancer to Goserelin.

The luteinizing hormone-releasing hormone/androgen receptor (LHRH/AR) pathway is a promising treatment target in a subgroup of female patients with triple-negative breast cancer (TNBC). However, very little is known about the efficacy of this strategy in male patients with TNBC. In this report, we describe a male patient with AR-positive TNBC who was successfully treated using an LHRH agonist after pretreatment with several lines of chemotherapy and achieved a durable response. We also review the existing evidence supporting LHRH- and AR-targeted therapy for this rare disease.

Ki 67 assessment in breast cancer in an Egyptian population: a comparative study between manual assessment on optical microscopy and digital quantitative assessment.

BACKGROUND: Breast cancer is by far the most frequent cancer among women. The proliferative index, Ki-67, is more and more taken into consideration for treatment decisions. However, the reliability of the established Ki-67 scoring is limited. Digital pathology is currently suggested to be a potential solution to Ki 67 assessment problems. METHODS: This is a retrospective and prospective study including 100 patients diagnosed with invasive breast cancer. Three senior pathologists have been asked to estimate the Ki-67 proliferative index for each of the 100 cases by examining the whole glass slides on optical microscope and providing a continuous score then a categorical score ('high' and 'low' Ki 67 index) using once 14%, once 20% as threshold indicative of high Ki67 status. Finally, a digital quantitative assessment of Ki67 was performed. RESULTS: A high inter-observer agreement was found when using optical microscopy for Ki 67 assessment, with correlation coefficient (CC) estimated at 0.878 (p value < 0.01). The overall agreement between manual and automated evaluation of Ki 67 was only substantial (CC estimated at 0.745 (p value < 0.01)). When using categorical scores, the inter-observers concordance was substantial using both cutoff points with kappa value estimated at 0.796 ([0.696-0.925] while using 14% as a cut off point and at 0.766 ([0.672-0.938] while using 20% as a cutoff point (p value < 0). The inter-observers agreement was better while using 14% as cutoff point. Agreement between manual and automated assessment of Ki 67 indices using both cutoff points was only substantial (Kappa estimated at 0.623, p value < 0.01). In comparison to automated assessment of Ki 67 index, while using 14% as a cutoff point, the overall tendency of all observers was to overestimate the Ki 67 values but to underestimate the proliferation index while using 20% as a cutoff point. CONCLUSION: Automated assessment of Ki 67 value would appear to be comparable to visual Ki 67 assessment on optical microscopy. Such study would help define the role of digital pathology as a potential easy-to use tool for a robust and standardized fully automated Ki 67 scoring.