The LAST guidelines in clinical practice: implementing recommendations for p16 use.

OBJECTIVES: To determine the impact of implementing p16 Lower Anogenital Squamous Terminology Standardization Project for HPV-Associated Lesions (LAST) guidelines, we compared p16 use and follow-up data before and after implementation of the guidelines. METHODS: We reviewed all cervical biopsy specimens diagnosed by two pathologists before and after implementation of the LAST guidelines and calculated the rate of and reason for p16 use across all biopsy specimens, high-grade squamous intraepithelial lesion (HSIL) detection, and follow-up. RESULTS: In total, 1,829 and 1,623 cervical biopsy specimens were reviewed in periods A and B, respectively. Overall p16 use increased from 2.8% to 6.2% (P < .001). Recommendations 2 and 4 increased from 0.16% and 0% of all cervical biopsy specimens in period A to 1.4% and 1.9% in period B, respectively (P < .0001). p16+ HSIL increased from 1.4% to 2.3% (P < .05). The positive predictive value of p16+ HSIL increased from 48% to 76% (P < .05). CONCLUSIONS: Implementation of the p16 LAST guidelines resulted in a significant increase in p16 use and a significant increase in the positive predictive value of p16+ HSIL.

Lynch Syndrome in patients with clear cell and endometrioid cancers of the ovary.

OBJECTIVE: Patients with Lynch Syndrome are at an increased risk for a variety of malignancies, including ovarian cancer. Ovarian cancers associated with Lynch Syndrome are predominantly clear cell or endometrioid in histology. Lynch Syndrome is characterized by germline mutations in mismatch repair (MMR) genes. The current study aims to assess the prevalence of loss of MMR expression in patients with endometrioid and clear cell ovarian carcinoma. METHODS: A retrospective review identified 90 patients with endometrioid and/or clear cell carcinomas. Slides made from tumor tissue microarray blocks were evaluated using immunohistochemical stains with antibodies against MLH1, PMS2, MSH2, and MSH6. Statistical analysis was performed. RESULTS: Seven of the 90 cases (7.8%) had loss of MMR expression. The mean age of patients with loss of MMR expression (47 years) was significantly younger than those with retained MMR expression (p=0.014). Loss of MMR expression was present in 20% of patients under the age of 53 with clear cell or endometrioid cancers. Genetic studies found that 3 of the 5 patients with loss of MMR expression carried mutations consistent with Lynch Syndrome; acquired hypermethylation of MLH1 was noted in one patient. Six of 7 patients (86%) whose tumors lacked MMR expression had synchronous or metachronous primary malignancies, a significantly greater prevalence than those with retained MMR expression (p<0.001). CONCLUSION: Patients under the age of 53 with clear cell or endometrioid ovarian carcinomas are at a clinically significant risk for loss of MMR expression and Lynch Syndrome; routine screening with immunohistochemical staining should be considered.