ABSTRACT
Serous, mucinous, endometrioid, and clear cell adenocarcinomas arise from reproductive organs of mullerian origin. Although the mutation of PTEN, a tumor suppressor, is known to be involved in tumorigenesis of endometrioid adenocarcinomas of the endometrium and ovary, the role of PTEN alteration in endometrioid adenocarcinoma of the cervix remains to be investigated. To elucidate the molecular pathogenesis of cervical adenocarcinoma and adenosquamous carcinoma, and in particular to examine the potential role of PTEN mutation in endometrioid-type cancer of the cervix, we analyzed 32 cervical adeno- or adenosquamous carcinomas (8 endometrioid adenocarcinomas, 14 mucinous adenocarcinomas and 10 adenosquamous carcinomas) for PTEN mutations and HPV infections. PTEN mutation was detected in 2 of 8 (25.0%) endometrioid cases, 2 of 14 (14.3%) mucinous cases, and none of 10 (0%) adenosquamous cases. HPV DNA was detected in 11 out of 18 (61.1%) PTEN wild-type adenocarcinomas and 8 out of 10 (80.0%) adenosquamous carcinomas. Among 11 HPV-negative adenocarcinomas, 40.0% (2/5) endometrioid cases and 33.3% (2/6) mucinous cases were shown to be PTEN mutated, while no cases (0/21) were PTEN-mutant in the remainder (i.e. adenosquamous carcinomas and HPV-positive adenocarcinomas). The current observations suggest that PTEN mutation is frequently detected in HPV-negative adenocarcinomas of the cervix and the most prevalent occurrence of PTEN mutation in endometrioid subtype is keeping with endometrial and ovarian carcinomas.
Subject(s)
Adenocarcinoma, Mucinous/genetics , Carcinoma, Endometrioid/genetics , Genes, Tumor Suppressor , Mutation/genetics , Phosphoric Monoester Hydrolases/genetics , Tumor Suppressor Proteins/genetics , Uterine Cervical Neoplasms/genetics , Adenocarcinoma, Mucinous/virology , Adult , Aged , Carcinoma, Adenosquamous/genetics , Carcinoma, Adenosquamous/virology , Carcinoma, Endometrioid/virology , DNA, Viral/genetics , Female , Humans , Middle Aged , PTEN Phosphohydrolase , Papillomaviridae/genetics , Papillomaviridae/isolation & purification , Papillomavirus Infections/genetics , Papillomavirus Infections/virology , Uterine Cervical Neoplasms/virologyABSTRACT
OBJECTIVE: This retrospective study was undertaken to identify selection criteria for nonradical surgery for early invasive adenocarcinoma of the uterine cervix. METHODS: Seventy-nine patients with surgically treated cervical adenocarcinomas (with invasion to 5 mm or less) were examined clinicopathologically. The evaluation of stromal invasion was conducted according to the FIGO (1995) staging system. RESULTS: The mean age was 46 (range: 29-73) years, and the median follow-up was 118 (9-348) months. Definitive treatment modalities included radical hysterectomy in 71 (89.9%) cases, modified radical hysterectomy in 2 (2.5%), and simple extrafascial hysterectomy without pelvic lymphadenectomy in 6 (7.6%). Postoperative adjuvant external radiation therapy was given to 5 (6.3%) patients. The histological subtypes were endocervical in 37 (46.8%) cases, endometrioid in 32 (40.5%), and adenosquamous in 10 (12.7%). Forty-one (51.9%) patients had lesions with up to 3 mm of stromal invasion; of these, 24 (58.5%) had lesions with up to 7 mm of horizontal extension (stage IA1). Thirty-eight (48.1%) patients had lesions with stromal invasion greater than 3 mm and no greater than 5 mm; of these, 4 had lesions with no wider than 7 mm of horizontal extension (stage IA2). Of 73 patients with pelvic lymphadenectomy, one (1.4%) tumor (depth: 5 mm; width: 15 mm) had node metastases. Parametrial involvement was present in one (1.4%) patient (lesion depth: 5 mm; lesion width: 16 mm). None had adnexal metastasis. Eighty-eight percent of the patients with stromal invasion up to 3 mm had well-differentiated adenocarcinoma, compared to 53% of the patients with lesions invading more than 3 mm. Of all of the patients, 5 (6.3%) patients who received curative radical hysterectomies had recurrences and died. Among 5 patients, one patient with central pelvic recurrence had a lesion invading to a depth of 3 mm and width of 7 mm, and the others had lesions with more than 3 mm of invasion and 15 to 36 mm of width. CONCLUSIONS: Patients with early invasive adenocarcinoma to a depth of 3 mm or less stromal invasion, including those who meet the criteria for FIGO stage IA1, may be treated with simple extrafascial hysterectomy without lymphadenectomy and oophorectomy.
Subject(s)
Adenocarcinoma/pathology , Adenocarcinoma/surgery , Hysterectomy/methods , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Adult , Aged , Female , Humans , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Prognosis , Retrospective Studies , Stromal Cells/pathologyABSTRACT
It is unclear which chromosome arms frequently show loss of heterozygosity (LOH) in adenocarcinoma of the uterine cervix. To identify such chromosomal arms, LOH on 52 different chromosome loci was examined using laser capture microdissection and PCR-LOH analysis in 25 common-type adenocarcinomas, comprising 13 cases of endocervical type, 12 cases of endometrioid type and 7 cases of adenoma malignum without the component of conventional endocervical-type adenocarcinoma (designated as "pure" form). In adenocarcinomas of endocervical type and endometrioid type, LOH was commonly detected on chromosome arms 17p (62% and 50%, respectively), 1p (33% and 67%) and 22q (40% and 33%). In addition, endocervical-type adenocarcinoma frequently (> or = 30%) showed LOH on 18p (71%), 19q (50%), 19p (38%) and 16q (38%), whereas endometrioid-type adenocarcinoma frequently showed LOH on 10q (43%) and 5q (40%). LOH was only sporadically detected on 9q, 18q, or 21q in 3 of 7 cases of "pure" adenoma malignum. In a case of coexistence of "pure" adenoma malignum and adenocarcinoma in situ (AIS), LOH on 1q, 5p, 11p, 17p, 18p and 18q was detected only in AIS. LOH was accumulated on a number of chromosome arms in the adenocarcinoma at the early developmental stage before stromal invasion. Chromosomal arms that are prone to show LOH appeared to differ between the 2 types of cervical adenocarcinoma. We could suggest that "pure" adenoma malignum is of clonal and neoplastic nature in view of the detection of LOH.