The Genomics of Colorectal Cancer in Populations with African and European Ancestry.

Black people have a higher incidence of colorectal cancer and worse survival rates when compared with white people. Comprehensive genomic profiling was performed in 46,140 colorectal adenocarcinoma cases. Ancestry-informative markers identified 5,301 patients of African descent (AFR) and 33,770 patients of European descent (EUR). AFR were younger, had fewer microsatellite instability-high (MSI-H) tumors, and had significantly more frequent alterations in KRAS, APC, and PIK3CA. AFR had increased frequency of KRAS mutations, specifically KRASG12D and KRASG13. There were no differences in rates of actionable kinase driver alterations (HER2, MET, NTRK, ALK, ROS1, and RET). In patients with young-onset colorectal cancer (<50 years), AFR and EUR had a similar frequency of MSI-H and tumor mutational burden-high (TMB-H) tumors, and strikingly different trends in APC mutations by age, as well as differences in MAPK pathway alterations. These findings inform treatment decisions, impact prognosis, and underscore the need for model systems representative of the diverse U.S. population. SIGNIFICANCE: KRAS (particularly KRASG12D/G13), APC, and PIK3CA were more frequently altered in AFR who had a lower frequency of MSI-H tumors. There were no differences in actionable kinase driver alterations. In young-onset colorectal cancer, both ancestries had a similar frequency of MSI-H/TMB-H tumors, but strikingly different trends in APC. See related commentary by Eng and Holowatyj, p. 1187. This article is highlighted in the In This Issue feature, p. 1171.

Role of prostate biopsy schemes in accurate prediction of Gleason scores.

OBJECTIVES: To determine whether improved prostate sampling by the extended biopsy scheme also improves the accuracy of the biopsy Gleason score (bGS). Because most prostate cancer cases are now detected at an early stage with a low prostate-specific antigen level, the bGS may be the most important factor in therapeutic decision-making. Sextant biopsy schemes had poor correlation with prostatectomy Gleason scores. Extended prostate biopsies have replaced the sextant scheme because of the former's greater cancer detection rate. METHODS: We identified 426 patients whose biopsy and prostatectomy specimens were reviewed at our center. To minimize the effect of stage migration, all patients before 1997 were excluded. Of the 426 included patients, 221 men had undergone sextant biopsy and 205 men extended biopsy before prostatectomy. The rate of grading concordance and the effect of different variables on the concordance rate was determined. RESULTS: The overall accuracy of the extended and sextant schemes was 68% and 48% (P <0.001), respectively. Upgrading of the bGS was significantly less likely with the extended scheme (17% versus 41%, P <0.001). The sextant biopsy was more likely to be upgraded for a bGS of 6 or less (44% versus 25%, P <0.002) and a bGS of 7 (14% versus 3%, P <0.02). On multivariate analysis, the biopsy scheme was the only independent predictor of accurate Gleason scoring (P <0.001) and age, prostate-specific antigen level, digital rectal examination findings, prostate size, clinical stage, and number of positive cores were not. CONCLUSIONS: The use of an extended prostate biopsy scheme significantly improves the correlation between the bGS and prostatectomy Gleason score and reduces the risk of upgrading to a worse Gleason group at prostatectomy.

Molecular diagnostics in melanoma.

Molecular pathology is rapidly evolving, featuring continuous technologic improvements that offer novel clinical opportunities for the recognition of disease predisposition, for identifying sub-clinical disease, for more accurate diagnosis, for selecting efficacious and non-toxic therapy, and for monitoring of disease outcome. Currently, the identification and prognosis of primary cutaneous melanoma is based on histologic factors (tumor depth and ulceration) and clinical factors (number of lymph node and/or distant metastases). However, metastasis can occur in patients with thin melanomas, and sentinel lymph node biopsy does not identify all patients at risk for distant metastasis. New markers exist that correlate with melanoma progression, which may aid in melanoma identification, prognostication, and detection of minimal residual disease/early recurrence. Moreover, not many therapeutic options exist for melanoma as no regimen prolongs survival. Emerging data with investigational therapies suggest that certain markers might play a crucial role in identifying patients who will respond to therapy or show utility in the monitoring the response to therapy. Herein, molecular diagnostics that can potentially benefit the individual melanoma patient will be discussed.