Strong correlation between molecular changes in endometrial carcinomas and concomitant hyperplasia.

OBJECTIVE: Endometrial cancer (EC) results from the accumulation of numerous genetic abnormalities contributing to the progression from hyperplasia to EC. Information on these various genetic changes has been primarily derived from studying groups of either hyperplasias or cancers.We evaluated both hyperplastic and EC tissue obtained from the same surgical specimens for KRAS mutations, microsatellite instability (MSI), and mismatch repair gene methylation, and results were correlated between the paired hyperplastic tissue and EC. The aim was to determine if molecular alterations appearing in ECs might also be present in the premalignant (hyperplastic) region of the tumor. METHODS: One hundred ninety-seven cases of EC with associated hyperplasia were evaluated. DNA samples were studied using primer sets for KRAS gene codons 12/13 and for MSI utilizing the Bethesda panel. Methylation testing was performed on specimens that were microsatellite unstable using the MRC Holland SALSA MS-MLPA methylation-specific DNA detection kit. RESULTS: Forty-one (20.8%) of 197 cancers demonstrated a KRAS mutation, with 35 (85.4%) of 41 accompanying hyperplasias also containing a KRAS mutation. Forty-five cancers (22.8%) were microsatellite unstable, with 38 (84.4%) of 45 accompanying hyperplasias also demonstrating instability. Of the 45 microsatellite unstable cancers, 28 (62.2%) demonstrated methylation in both the cancer and the accompanying hyperplasia, whereas 9 pairs (20%) showed no methylation for either the cancer or hyperplasia. CONCLUSIONS: Approximately 95% of endometrial specimens demonstrated identical molecular findings regarding KRAS mutation and microsatellite stability in the paired cancer and hyperplastic tissue. The same methylation pattern was found in 82.2% of the studied paired samples. Our findings strongly suggest that the molecular changes of KRAS mutation, MSI, and methylation occur early in the neoplastic process. We propose that endometrial biopsies revealing only hyperplasia should be studied for these molecular alterations as an indicator of possible early carcinogenesis.

Rice body formation without rheumatic disease or tuberculosis infection: a case report and literature review.

Rice body formation is an uncommon inflammatory disorder associated with systemic disorders such as rheumatoid arthritis and tuberculosis infection. The pathophysiology of rice bodies is poorly understood. We describe a case of rice body formation in a 51-year-old male who presented with pain and swelling of the left wrist. The patient had no previous history of rheumatic disease, joint trauma, or infectious disease. He underwent a radical tenosynovectomy and had immediate improvement of symptoms. Despite extensive evaluation, the etiology of the rice bodies could not be identified. An increasing number of case reports have described rice body formation without a known cause suggesting an alternative, unidentified method of pathogenesis. We describe a unique case of rice body formation and a review of the literature with emphasis on theories of pathogenesis, diagnostic methods, and treatment.

Microsatellite instability and DNA methylation of endometrial tumors and clinical features in young women compared with older women.

INTRODUCTION: Molecular genetic changes in endometrial cancers are important to identify possible family cancer syndromes and thus, to facilitate appropriate screening. Most studies in this regard have focused primarily on young women. We have assayed cancers for microsatellite instability (MSI) and DNA methylation from a large group of patients younger than 50 years and a comparable group of older women. We obtained personal and medical histories of the patients and their family cancer histories. METHODS: The Bethesda panel of markers was used for the detection of MSI. Methylation status of mismatch repair genes was ascertained using the methylation-specific DNA detection kit SALSA MS-MLPA No. ME011. RESULTS: There were 101 patients younger than 50 years and 112 older women. The 2 age groups did not differ in the percentage of patients who were obese, carried a diagnosis of diabetes, or previously had another cancer. The younger patients were more likely to be nulliparous, whereas the older patients were more likely to have hypertension. Among the younger group, 21 (20.8%) tumors revealed MSI, and 13 (61.9%) of these were unmethylated. For the older women, 35 (31.2%) had MSI tumors, and only 6 (17.1%) of these were unmethylated. Young women with a family history of a hereditary nonpolyposis colorectal cancer-related cancer were more likely to have a tumor revealing MSI and no methylation, but family history was less helpful in older women in this regard. CONCLUSION: We did not find personal risk factors or a history of an additional cancer to be different between the 2 age groups. The combination of MSI testing and DNA methylation studies resulted in the identification of presumptive hereditary nonpolyposis colorectal cancer syndrome in approximately 13% of women with endometrial cancer presenting at age younger than 50 years and in approximately 5% of older women. Family history was more helpful with younger women than with older women.