An Introduction to Continuity, Extrema, and Related Topics by Adler R.J.

By Adler R.J.

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38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48. 49. 50. 51. 52. 53. copathologic and molecular study of two cases. Int J Gynecol Pathol 21:268–272, 2002. Kounelis S, Jones MW, Papadaki H, et al: Carcinosarcomas (malignant mixed mullerian tumors) of the female genital tract: comparative molecular analysis of epithelial and mesenchymal components. Hum Pathol 29:82–87, 1998. Abeln EC, Smit VT, Wessels JW, et al: Molecular genetic evidence for the conversion hypothesis of the origin of malignant mixed mullerian tumours.

Endometrioid carcinoma (EMCA) contains mutations in β-catenin and PTEN. Although the molecular genetic changes in clear cell carcinoma (CCCA) have not been extensively studied, mutations in PI3CA have been detected in approximately 20% of cases. Mucinous carcinoma (MCA) is characterized by mutations in KRAS in most cases. 19 Oncogenic (activating) mutations in BRAF and KRAS result in constitutive activation of this pathway and contribute to neoplastic transformation. 20 Mutations in BRAF and KRAS, therefore, were found in about two thirds of low-grade invasive serous carcinomas and atypical proliferative tumors and in noninvasive MPSCs, their putative precursors, but neither of the genes was mutated in high-grade serous carcinomas.

Four genes have been associated with HNPCC thus far, and clinical genetic testing is available for all of these genes. Interventions in women who carry BRCA1, BRCA2, or HNPCC mutations include intensive cancer screening, chemoprevention, and prophylactic surgery. In BRCA1 and BRCA2 mutation carriers, prophylactic bilateral salpingo-oophorectomy has been shown to reduce the risk of ovarian cancer by 80% to 90% when compared with gynecologic surveillance to detect early-stage ovarian cancer. In the United States, bilateral salpingo-oophorectomy is considered the standard of care.

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