title: Postmenopausal status, hypertension and obesity as risk factors for malignant transformation in endometrial polyps.
abstract: OBJECTIVE
  We analyzed clinical data and pathological features of six cases of malignant endometrial polyps, to compare these with other examples reported in literature and to define the features of endometrial cancer arising in polyps. Moreover, to clarify the mechanisms of carcinogenesis in malignant endometrial polyps we examined the expression of cyclooxygenase-2 (COX-2), P53 and Ki 67 and their relationships with clinicopathologic characteristics.
  
  
  METHODS
  The surgical pathology files of the Pathology Department of Parma University were searched for cases of endometrial polyps with nests of endometrial carcinomas, from the years 2002-2005. Clinical records, histological slides of endometrial curetting, hysterectomy with salpingo-oophorectomy specimens and pelvic lymph nodes were reviewed in each case. The main pathological features analyzed were histological types of endometrial cancer and the stage of development of neoplasm. The presence of other malignancies in the genital tract were also considered. Immunohistochemical staining was done using antibodies COX-2, p53 and Ki 67.
  
  
  RESULTS
  In our study, all malignant endometrial polyps had been detected in postmenopausal women. The majority of our patients with malignant endometrial polyps had risk factors for the development of endometrial carcinoma such as hypertension, obesity and unopposed estrogen therapy. Unlike other studies, no patients had a history of previous breast carcinoma and Tamoxifen treatment. The most common subtypes of endometrial carcinoma in malignant polyps are endometrioid carcinoma and serous papillary carcinoma. Endometrial carcinoma arising in endometrial polyps is an early endometrial carcinoma with good prognosis, except for papillary serous carcinoma, which can be associated with multiple omental involvement, despite low stage of development in the uterus. Immunohistochemical study showed that COX-2 expression was found in cytoplasm of tumor cells and this was elevated in all cases, independently of the grade and the stage of development of the malignancy, histological subtype and deep invasion of myometrium. P53 and Ki 67 expression, detected in the nuclei of neoplastic cells, was not correlated with COX-2 immunoreactivity, but these markers were associated with more advanced stage, grading, and histologic subtypes of tumor.
  
  
  CONCLUSIONS
  Postmenopausal status, hypertension, obesity could all be considered as risk factors for carcinomatous transformation within endometrial polyps in women without a history of breast carcinoma and Tamoxifen treatment. However, our series is small (only six cases considered) and further studies are necessary to confirm this hypothesis. In the current study, immunohistochemical data reveal that COX-2 expression may be associated with the carcinogenesis in endometrial carcinomas arising in endometrial polyps, but this antibody is not correlated with tumor aggressiveness, P53 and Ki 67 expression. P53 and Ki 67 overexpression, instead, are associated with advanced stage, histologic subtype and deep myometrial invasion of neoplasm.
authors.affiliation: Department of Pathology and Medicine of Laboratory, Section of Pathology, Parma University, Viale A. Gramsci 14, 43100 Parma, Italy. giovanna.giordano@unipr.it
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giordano
authors.forename: Letizia
authors.initials: L
authors.lastname: Gnetti
authors.forename: Carla
authors.initials: C
authors.lastname: Merisio
authors.forename: Mauro
authors.initials: M
authors.lastname: Melpignano
mesh_terms: D000368:Aged; D018269:Carcinoma, Endometrioid / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications*; D019394:Ki-67 Antigen / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D011127:Polyps / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D017698:Postmenopause; D012307:Risk Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014591:Uterine Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen; D008565:Membrane Proteins; D016159:Tumor Suppressor Protein p53; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human