Cancer Targeted Therapy Strategy: The Pathologist's Perspectives.

The effectiveness of new personalized treatment procedures in oncology is based on the fact that certain tumors exhibit specific molecular features. More in detail, neoplastic tissues of patients should display a specific biomarker, most often a specific genetic alteration and/or under/overexpression of a definite protein, that could be the target of its respective drug. Immunohistochemical and molecular analyses, which usually include examination of nucleic acids from either tissues or fluids, are common tests to define the status of a tumor. This review focuses on the pathologist's role in carefully controlling pre- analytic procedures and standard operating procedures that are a crucial prerequisite to reach reliable and reproducible results. Six paradigmatic applications of targeted therapy, for which pathological diagnosis plays a fundamental role, are summarized. Traditional and next-generation sequencing are also addressed from the pathologist's perspective as well as the importance pathologists have in this shift to more accurate definition of disease risk and prognostication of therapy response in the personalized medicine era.

KRAS and BRAF mutational status in colon cancer from Albanian patients.

BACKGROUND: Numerous clinical studies have shown that anti-EGFR therapies are effective only in a subset of patients with colorectal cancer. Mutations in the KRAS and BRAF genes have been confirmed as negative predictors of the response to EGFR-targeted therapies.In this study we evaluated KRAS and BRAF status in 159 colorectal cancer samples obtained from the University of Tirana. METHODS: We evaluated KRAS mutations in codons 12, 13, 61, 146 and in codon 600 of BRAF by direct sequencing. 90 patients were male (57%) and 69 female (43%); the patients' ages ranged from 17 to 85 (median 61.7). 24 patient were stage I, 36 stage II, 84 stage III and 15 stage IV. RESULTS: Out of the 159 cases, 28 (17,6%) showed KRAS mutation (13 G12D, 4 G12C, 4 G12V, 3 G12A, 2 G13 D, 1 G12S and 1 A146T), and 10 (6,3%) showed BRAF mutation (all V600E). No significant correlations between KRAS and BRAF mutations and various clinicopathological parameters was found.This is the first report of KRAS and BRAF status in Albanian patients with colorectal carcinoma (CRC) and though the relatively small sample size might not provide enough statistics power. CONCLUSIONS: The results of KRAS and BRAF mutation analysis could be used in the selection of patients for anti-EGFR therapy. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_187.

Classification of patients with breast cancer according to Nottingham prognostic index highlights significant differences in immunohistochemical marker expression.

BACKGROUND: Prognosis and treatment of patients with breast carcinoma of no special type (NST) is dependent on a few established parameters, such as tumor size, histological grade, lymph node stage, expression of estrogen receptor, progesterone receptor, and HER-2/neu, and proliferation index. The original Nottingham Prognostic Index (NPI) employs a three-tiered classification system that stratifies patients with breast cancer into good, moderate, and poor prognostic groups. The aim of our study was to use robust immunohistochemical methodology for determination of ER, PR, HER-2/neu, Ki-67, p53, and Bcl-2, and to observe differences in the expression of these markers when patients are stratified according to the original, three-tiered Nottingham Prognostic Index. METHODS: Paraffin blocks from 120 patients diagnosed with breast carcinoma, NST, were retrieved from our archive. Cases included in the study were female patients previously treated with modified radical mastectomy and axillary dissection. RESULTS: Our study demonstrates that expression of markers of good prognosis, such as ER, PR, and Bcl-2, is seen with higher frequency in good and moderate NPI groups. In contrast, overexpression of HER-2/neu, a marker of adverse prognosis, is more frequent in moderate and poor NPI groups. High proliferation index, as measured by Ki-67, is seen in moderate and poor NPI groups, whereas low proliferation index is seen in good NPI groups. CONCLUSIONS: These data confirm that the original, three-tiered NPI statistically correlates with the expression of prognostic immunohistochemical markers in breast carcinoma NST.