Anatomic Pathology Selected Abstracts, 2/15

Create PDF

MED12 and HMGA2 mutations: independent genetic events in uterine leiomyoma and leiomyosarcoma

Recent identification of somatic MED12 mutations in most uterine leiomyomas brings a new perspective to the study of the tumorigenesis of leiomyomas. The authors were particularly interested in the correlation of MED12 and HMGA2 gene products in leiomyomas and leiomyosarcomas with and without MED12 mutations. To address these issues, they examined MED12 mutations in a large cohort of usual type leiomyomas (178 cases) and uterine leiomyosarcomas (32 cases). They found that 74.7 percent (133 of 178) of leiomyomas had MED12 mutations, which was consistent with several independent studies. In contrast, only 9.7 percent (three of 32) of leiomyosarcomas harbored MED12 mutations. Expression analysis by Western blot and immunohistochemistry revealed that those leiomyomas with complex MED12 mutations had significantly lower protein products than the matched myometrium. Interestingly, most leiomyosarcomas without MED12 mutations also had very low levels of MED12 expression in comparison to the matched myometrium. These findings suggest a potential functional role for MED12 in benign and malignant uterine smooth muscle tumors. When the authors further examined the HMGA2 expression in all leiomyomas and leiomyosarcomas, they found that HMGA2 overexpression was present exclusively in those leiomyomas with no MED12 mutation, accounting for 10.1 percent (18 of 178) of total leiomyomas and 40 percent (18 of 45) of non-MED12 mutant leiomyomas. Twenty-five percent (eight of 32) of leiomyosarcomas had HMGA2 overexpression, and no MED12 mutations were found in HMGA2-positive leiomyosarcomas. These findings strongly suggest that MED12 mutations and HMGA2 overexpression are independent genetic events that occur in leiomyomas, and they may act differently in the tumorigenesis of uterine leiomyomas.

Bertsch E, Qiang W, Zhang Q, et al. MED12 and HMGA2 mutations: two independent genetic events in uterine leiomyoma and leiomyosarcoma. Mod Pathol. 2014;27(8):1144–1153.

Correspondence: Dr. T. Kurita at t-kurita@northwestern.edu or Dr. J. J. Wei at jianjun-wei@northwestern.edu

Human papillomavirus genotyping and p16 expression as prognostic factors in carcinoma of the anal canal

Carcinomas of the anal canal are strongly associated with human papillomavirus. Expression of p16 is used as a surrogate marker of such infection. The authors conducted a retrospective study in which they evaluated human papillomavirus (HPV) genotyping and p16 expression as prognostic markers of overall survival and disease-specific survival in patients diagnosed with American Joint Committee on Cancer stages I to III carcinoma of the anal canal. HPV genotyping polymerase chain reaction (high-risk subtypes 16, 18, 31, 33, 45, 52, and 58) and immunohistochemical expression of p16 were analyzed using paraffin-embedded tumor biopsies from 143 anal carcinomas. The patients were treated with combined chemoradiotherapy or radiotherapy alone. HPV16 was detected in 81 percent of the tumors, followed by HPV33 (5.1 percent), HPV18 (2.2 percent), and HPV58 (0.7 percent). P16 positivity was found in 92.9 percent of the tumors. In univariable survival analysis, HPV positivity was significantly correlated with improved overall survival (74 percent versus 52 percent; P=0.036) and disease-specific survival (84 percent versus 52 percent; P=0.002), and p16 positivity was significantly correlated with improved overall survival (76 percent versus 30 percent; P=0.001) and disease-specific survival (85 percent versus 30 percent; P<0.001). In multivariable Cox analysis that included HPV status, p16 status, gender, T stage, N stage, and treatment, p16 positivity remained an independent prognostic factor for overall survival (hazard ratio [HR], 0.07; 95 percent confidence interval [CI], 0.01–0.61; P=0.016) and disease-specific survival (HR, 0.07; 95 percent CI, 0.01–0.53; P=0.011). The authors concluded that p16 positivity is an independent prognostic factor for overall and disease-specific survival in patients with American Joint Committee on Cancer stages I to III carcinoma of the anal canal.

Serup-Hansen E, Linnemann D, Skovrider-Ruminski W, et al. Human papillomavirus genotyping and p16 expression as prognostic factors for patients with American Joint Committee on Cancer stages I to III carcinoma of the anal canal. J Clin Oncol. 2014;32:1812–1817.

Correspondence: Dr. Eva Serup-Hansen at eva.serup-hansen@regionh.dk