[Biomarker for colorectal cancer] - Lynch Syndrome/MSI/KRAS/BRAF

[Biomarker for colorectal cancer]

Abstract
Discovery of usable molecular biomarkers is the step closer to a realization of personalized therapy for patients with colorectal cancer(CRC). Herein we present an update of the most recent data on promising biological prognostic and/or predictive markers, including microsatellite instability(MSI) and KRAS/BRAF mutations. Additionally, we propose a new genetic classification for CRC based on MSI and KRAS/BRAF mutation status (a 2 x 3 matrix). The 2 x 3 matrix is constructed of 6 cells that are made by [MSI/non-MSI] x [BRAF mutant/KRAS mutant/wild type of the both genes].

All of CRC including Lynch syndrome could be classified without overlapping into the 6 cells. More interestingly, each cell has each promising biological prognostic and/or predictive feature, which will help clinicians to make personalized treatment strategy for each CRC patient.

(Apr 2012) Commentary: Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology

Link between endometriosis and ovarian-cancer subtypes : The Lancet Oncology

"Previous large epidemiological studies have attempted to identify benign gynaecological disorders that predispose to the development of epithelial ovarian cancer. The only disorder that has been repeatedly1—4 (although not universally5) associated with this cancer is endometriosis. Results of some of these studies have suggested a specific link with endometrioid and clear-cell ovarian cancers, but until now none had the power to allow definitive subgroup analysis based on a contemporary definition of histological subtype.

 

In a study reported in the Lancet Oncology, Celeste Leigh Pearce and colleagues6 assessed self-reported endometriosis data from 13 pooled case—control studies in the Ovarian Cancer Association Consortium (OCAC). They confirm that a history of endometriosis is significantly associated with an increased risk of clear-cell (odds ratio 3·05, 95% CI 2·43—3·84) and endometrioid (2·04, CI 1·67—2·48) ovarian cancers, and for the first time show an association with low-grade serous ovarian cancer (2·11, 1·39—3·20). No association was noted between endometriosis and high-grade serous, mucinous, serous borderline, or mucinous borderline ovarian cancers.

 

With more than 23 000 participants (7911 with a diagnosis of ovarian cancer), the main strengths of this study are its statistical power and its robust methods. Incidences of reported endometriosis differ substantially between the pooled studies. Although clinicopathological and genetic differences between the populations could reasonably be expected, importantly there was no significant heterogeneity of the association with histological subtype in the different studies.

The main truly novel finding is an association between a history of endometriosis and low-grade serous ovarian cancer. Perhaps surprisingly, serous borderline tumours (from which invasive low-grade serous ovarian cancers are believed to arise7) are not also associated with a history of endometriosis.

abstract: KRAS mutations in ovarian low-grade endometrioid adenocarcinoma: association with concurrent endometriosis (study of KRAS/BRAF mutations)

Summary

The association between ovarian endometrioid adenocarcinoma and endometriosis is well established. However, not all endometrioid adenocarcinomas are directly related to endometriosis, and it has been suggested that there may be clinicopathologic differences between endometriosis-positive and endometriosis-negative tumors. Molecular alterations in endometrioid adenocarcinoma include KRAS and BRAF mutations, but the incidence of these abnormalities in previous reports has been highly variable (0%-36% and 0%-24%, respectively).....

Keywords

• Ovary;
• Endometrioid;
• Adenocarcinoma;
• Endometriosis;
• Molecular

preview: RAF around the Edges — The Paradox of BRAF Inhibitors — NEJM

RAF around the Edges — The Paradox of BRAF Inhibitors

N Engl J Med 2012; 366:271-273January 19, 2012

This article has no abstract; the first 100 words appear below.

The recent success of BRAF inhibitors represents a great stride forward for melanoma research. When used to treat patients with melanoma who harbor the BRAF V600E mutation, these inhibitors lead to the remission of even advanced lesions. However, resistance to BRAF inhibitors emerges within months. Of added concern is the development of secondary tumors, most commonly cutaneous squamous-cell carcinomas and keratoacanthomas, in response to BRAF inhibition.¹ In this issue of the Journal, Su et al. found that BRAF inhibition leads to increased MAPK (mitogen-activated protein kinase) signaling and secondary tumor development when another oncogene, HRAS, is activated.² This is due . . .

(original article/abstract) RAS Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors — NEJM