Menopausal hormones and risk of ovarian cancer

OBJECTIVE: The objective of this study was to determine if use of menopausal hormones was associated with ovarian cancer and if risk varied by type of hormone used. STUDY DESIGN: Data from a population-based, case-control study of ovarian cancer in North Carolina (364 cases, 370 controls, all postmenopausal) were analyzed to evaluate the relationship between menopausal hormones and ovarian cancer. Logistic regression analyses were used to calculate odds ratios (OR) and 95% CIs associated with various patterns of hormone use. RESULTS: Ovarian cancer cases were more likely than controls to report long-term use (>or=10 years) of unopposed estrogens (OR 2.2; 95% CI 1.2-4.1). No relationship was observed for estrogen always used with progestin. CONCLUSION: Hormone replacement therapy used according to current recommendations should not increase risk of ovarian cancer; however, clinicians should be aware of possible increased risk among women with a long history of estrogen replacement therapy.     

Evidence for a Common Etiology for Endometrial Carcinomas and Malignant Mixed Mullerian Tumors

Objective.To elucidate factors linked to the development of malignant mixed mullerian tumors (MMMT) and determine whether the risk factor profile for these tumors corresponds with that for the more common endometrial carcinomas.Methods.A multicenter case–control study of 424 women diagnosed with endometrial carcinoma, 29 women diagnosed with MMMT, and 320 community controls was conducted. Review of pathological reports and slides was performed to classify cases by histological type. All participants were asked to respond to a questionnaire which ascertained information on exposure to factors postulated to be linked to the development of uterine tumors.Results.Women with endometrial carcinomas and MMMTs were similar with respect to age and educational attainment. Women diagnosed with MMMTs were more likely than those diagnosed with carcinomas to be of African–American descent (28% vs 4%;P= 0.001). Weight, exogenous estrogen use, and nulliparity were related to risk of both tumor types. Marked obesity was associated with a 4.8-fold (95% CI = 3.0,7.6) increase in risk of carcinoma and a 3.2-fold (95% CI = 1.1,9.1) increase in risk of MMMT development. Use of exogenous estrogens increased the odds of developing carcinomas by 2-fold (95% CI = 1.3,3.2) and that of developing MMMTs by 1.8-fold (95% CI = 0.57,5.5). Nulliparity was associated with a 2.9-fold (95% CI = 1.9,4.8) increase in risk of carcinomas and a 1.7-fold (95% CI = 0.53,5.6) increase in risk of MMMTs. Oral contraceptive use protected against the development of both carcinomas (OR = 0.39; 95% CI = 0.26,0.58) and MMMTs (OR = 0.76; 95% CI = 0.25,2.3). Current smokers were at a reduced risk of developing endometrial carcinomas (OR = 0.34; 95% CI = 0.21,0.55) and MMMTs (OR = 0.57; 95% CI = 0.15,2.3), while former smokers were at an increased risk of MMMT (OR = 2.7; 95% CI = 1.1,6.8) but not carcinoma development (OR = 0.81; 95% CI = 0.56,1.2).Conclusion.Results from this study suggest that MMMTs and carcinomas have a similar risk factor profile. This observation is compatible with the hypothesis that the pathogenesis of these two histological types of uterine tumors is similar.     

Inverse correlation between RASSF1A hypermethylation, KRAS and BRAF mutations in cervical adenocarcinoma

OBJECTIVE: Although the incidence of cervical adenocarcinoma is increasing, few genetic and epigenetic changes in its progression have been described. We hypothesized that RASSF1A methylation and KRAS and BRAF mutations may play an important role in cervical adenocarcinoma. METHODS: Archival primary carcinoma tissues (n=258) in uterine cervix consisting cervical adenocarcinomas (n=115) and squamous cell carcinomas (n=143) were evaluated for activating mutations of BRAF and KRAS and promoter hypermethylation of RASSF1A using methylation specific PCR and specific sequence analysis. HPV E7 Type-specific PCR was used for HPV-16 and -18 status. RESULTS: KRAS mutations were found in 16 adenocarcinomas (13.9%), while BRAF mutations were found in 5 (4.3%). RASSF1A methylation was found in 27 adenocarcinomas (23.5%) and inversely correlated with KRAS and/or BRAF mutation (p=0.002) in cervical adenocarcinoma. In cervical squamous cell carcinomas, KRAS mutations were detected only in 1 (0.7%) cases and RASSF1A hypermethylation was detected in 2 (1.4%). The frequency of KRAS mutation and RASSF1A methylation were significantly different between adenocarcinomas (P<0.001) and squamous cell carcinomas (P<0.001). Neither KRAS mutation nor RASSF1A methylation were associated with HPV status. RASSF1A hypermethylation and KRAS mutations and BRAF mutations are inversely correlated and play an important role in the development of adenocarcinomas. CONCLUSIONS: These results are suggesting that these two histological types of cervical cancer arise through different molecular pathways in tumor development. Different genetic/epigenetic alterations may explain the possible different therapeutic responsiveness between adenocarcinoma and squamous cell carcinoma of uterine cervix seen in clinic.     

Association of the NAD(P)H: quinone oxidoreductase C609T polymorphism and the risk of cervical cancer in Japanese subjects

OBJECTIVE: In this study, genetic polymorphisms, NQO1 C609T, GSTM1 positive/null, and GSTT1 positive/null, were examined with reference to cervical cancer risk in a population-based incident case-control study in Japanese. METHODS: The cases comprised 131 cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled from 320 healthy women who underwent a health checkup. RESULTS: The cervical cancer risk was substantially elevated with smoking for all cases, SCC cases, and ADC/ADSC cases (OR = 4.50, 95% CI = 2.48-8.17, P < 0.001; OR = 5.68, 95% CI = 2.99-10.78, P < 0.001; and OR = 2.57, 95% CI = 1.09-6.08, P = 0.032; respectively). The frequency of the NQO1 609TT genotype, reported to be associated with null enzyme activity, was higher in individuals with all cases and SCC than in the healthy controls (OR = 1.97, 95% CI = 1.06-3.66, P = 0.032; and OR = 2.42, 95% CI = 1.21-4.82, P = 0.012; respectively), but not in ADC/ADSC cases. Analysis of polymorphisms for GSTM1 and GSTT1 showed no significant differences between cervical cancer patients and controls. In stratification analysis, significant elevated risk of all cases and SCC was associated with the NQO1 609TT genotype among nonsmokers (OR = 2.15, 95% CI = 1.08-4.30, P = 0.030; and OR = 2.83, 95% CI = 1.21-6.31, P = 0.011; respectively), but not smokers. No gene-gene interaction was observed in our case subjects. CONCLUSION: This is the first report that the NQO1 gene might be important in relation to the risk of squamous cell carcinoma of the cervix.     

Hyperestrogenism: a relevant risk factor for the development of cancer from endometriosis

OBJECTIVE: Endometriosis is extremely common in developed countries. Obesity is a major health concern and may cause hyperestrogenism. Hormonal replacement, particularly unopposed estrogens after hysterectomy, is becoming popular. Because endometriosis is ectopic endometrium, hyperestrogenism (either endogenous or exogenous) may cause hyperplasia or transformation into cancer. This study was conducted to describe the main clinical and pathologic features of malignancies in endometriosis and define the treatment and outcome and to compare patients who had cancer arising in endometriosis with patients who had endometriosis but no cancer. METHODS: Patients who had tumors from endometriosis diagnosed from 1986 to 1997 were analyzed retrospectively. Each patient was matched with two control patients (endometriosis without cancer) treated during the same study interval. Clinical and epidemiologic variables were compared to identify risk factors for the development of cancer. RESULT: We identified 31 patients with cancer developing from endometriosis. Fifteen women were obese, 9 had a history of endometriosis, and 9 were taking unopposed estrogen. Endometrioid adenocarcinoma was the most common histologic type (16 patients). When the patients with cancer were compared with controls, no significantly higher risk for the development of cancer was found with prolonged use of unopposed estrogens or with higher body mass index, but a trend was observed. When obesity and use of unopposed estrogens were considered together, the difference was statistically significant (P = 0.05). CONCLUSION: Hyperestrogenism, either endogenous or exogenous, is a significant risk factor for the development of cancer from endometriosis. The prevalences of endometriosis, obesity, and use of hormonal replacement therapy in women in developed countries are increasing, and this trend justifies the assumption that cancer developing in endometriosis might become more common in the future.     

Prognosis and treatment of primary adenocarcinoma and adenosquamous cell carcinoma of the uterine cervix.

PURPOSE: To evaluate a cohort of women with primary invasive carcinomas of the uterine cervix, and to compare the biological characteristics and behavior of a cohort of adenosquamous carcinomas with a cohort of adenocarcinomas and squamous cell carcinomas. METHODS: One hundred and fourteen cases of primary invasive cervical carcinoma presenting between 1 January 1987 and 31 December 1997 were studied. Sixteen (14%) women with adenosquamous cell carcinomas and eight (7%) adenocarcinomas were compared with 90 (79%) women with squamous cell carcinomas. Patients with Stage Ib and IIa were treated by radical hysterectomy and pelvic lymph node dissection. All patients with stage IIb and over were treated by radiation. Patients with bulky, large, barrel-shaped lesions were selected for treatment by a combination of radiation and extrapelvic hysterectomy. RESULTS: The corrected survival rate for stage Ib patients with adenosquamous cell carcinoma was only 27.2%, compared with a 92.2% corrected survival rate for squamous cell, and a 100% corrected survival rate for adenocarcinoma. CONCLUSION: There is a higher proportion of adenosquamous cell and adenocarcinoma of the cervix than generally appreciated. The epidemiological risk factors associated with adenosquamous carcinomas of the cervix are more similar to those of squamous cell carcinomas than of adenocarcinomas. The survival difference between two groups is explained by effects of clinical stage, nodal spread, and vascular space involvement.     

Association of XRCC1 Arg399Gln and OGG1 Ser326Cys polymorphisms with the risk of cervical cancer in Japanese subjects

OBJECTIVE: In this study, genetic polymorphisms, XRCC1 Arg399Gln and OGG1 Ser326Cys were examined with reference to cervical cancer risk in a population-based incident case-control study in Japan. METHODS: The cases comprised 131 cervical cancer patients: 87 cases with squamous cell carcinoma (SCC) and 44 with adenocarcinoma (ADC) or adenosquamous carcinoma (ADSC). Controls were sampled from 320 healthy women who underwent a health checkup. RESULTS: The frequency of the XRCC1 399GlnGln genotype was higher in individuals with adenocarcinoma/adenosquamous carcinoma than in the healthy controls (OR = 2.98, 95% CI = 1.11-8.01, P = 0.030). However, no association was demonstrated in SCC. Analysis of OGG1 Ser326Cys polymorphism showed no significant differences between cervical cancer patients and controls. In stratification analysis, significant elevated risk of adenocarcinoma/adenosquamous carcinoma was associated with the XRCC1 399GlnGln genotype among nonsmokers (OR = 3.85, 95% CI = 1.28-11.59, P = 0.017), but not among smokers. No gene-gene interaction was observed in our case subjects. CONCLUSION: This is the first report that the XRCC1 Arg399Gln polymorphism might be important in relation to the risk of adenocarcinoma/adenosquamous carcinoma of the cervix.     

汉族妇女中p21 codon31单核苷酸多态性与宫颈癌易感性关系的研究

目的:研究汉族妇女中p21codon31单核苷酸多态性与宫颈癌易感性之间的关系。方法:用DNA抽提试剂盒从研究对象的外周血标本中抽提基因组DNA,其中宫颈癌患者226例(鳞状细胞癌215例,宫颈腺癌11例),正常对照组196例;用错配扩增突变检测PCR的方法测定p21codon31单核苷酸多态基因型。结果:宫颈鳞状细胞癌患者的p21codon31AGA(精氨酸)等位基因频率显著高于对照组(37.0%vs 24.0%,P<0.05,OR=1.9,95%CI=1.0~3.4);宫颈鳞状细胞癌与对照组之间的AGA/AGA、AGA/AGC和AGC/AGC等位基因型的分布差异有统计学意义,其中AGA/AGA(OR=2.5,95%CI=1.4~4.5)和AGA/AGC(OR=1.8,95%CI=1.6~2.8)等位基因型在宫颈鳞状细胞癌中的频率显著高于对照组。宫颈腺癌与对照组之间p21codon31单核苷酸多态性分布没有显著差异。结论:p21codon31AGA(精氨酸)等位基因可能是汉族妇女患宫颈鳞状细胞癌的一个危险因素。     

In situ adenocarcinoma and squamous carcinoma of uterine cervix. Pathological and immunohistochemical analysis with cytokeratin 13

OBJECTIVES: The aim of the study was the pathological and immunohistochemical analysis of cytokeratin 13 (CK13) in intraepithelial cervical tumors. STUDY DESIGN: We studied 415 in situ squamous carcinomas and 13 in situ mucinous cervical type adenocarcinomas of the uterine cervix. All patients underwent laser cervical conization and had a follow-up ranging 12-135 months. RESULTS: 3% of the squamous carcinoma patients recurred during the follow-up period, while the percentage of recurrence of in situ adenocarcinoma patients was 7.6%. We observed positive surgical edges in 46.1% of glandular tumors, and in 5% of squamous tumors. The percentage of recurrence was high among the cases with positive borders independently from their histopathologic type (14.3% in the squamous carcinomas versus 50% in the adenocarcinomas), compared to cases with negative edges (2.3% in the squamous carcinomas versus 0% in the adenocarcinomas). We observed CK13 positive staining in cervical squamous tumors and in mucinous cervical type adenocarcinomas, while there was no positive staining in non-neoplastic cervical glandular elements. CONCLUSION: CK13 positive immunostaining among in situ squamous and in situ mucinous cervical type adenocarcinoma cases adds additional evidence to data supporting a common origin of the two lesions.     

Risk Factors for Epithelial Borderline Ovarian Tumors: Results of a Swedish Case–Control Study

OBJECTIVE: Borderline ovarian tumors have a favorable prognosis. Previous epidemiological studies indicate common risk factors for invasive epithelial ovarian cancers and borderline tumors, but it remains unresolved whether these tumors are precursors of invasive cancers or a separate disease entity. The objective of this population-based case-control study conducted in 1993-1995 was to examine reproductive and other factors in relation to the risk of borderline ovarian tumors. METHODS: Subjects were 193 histologically verified incident epithelial borderline tumor cases and 3899 randomly selected controls aged 50-74 years, whose data were collected through mailed questionnaires. Risk estimates were calculated by unconditional logistic regression. RESULTS: Ever parous women were at reduced risk, with odds ratios of 0.44 (95% confidence interval (CI) 0.26-0.75) for serous and 0.63 (95% CI 0.34-1.19) for mucinous tumors. No clear trends emerged for age at first birth, at menarche, and at menopause. Lactation reduced tumor risk. Oral contraceptive ever use conferred no protection, with odds ratios of 1.40 (95% CI 0.87-2.26) for serous and 1.04 (95% CI 0.61-1.79) for mucinous tumors. The odds ratio for serous tumors following unopposed estrogen ever use was 2.07 (95% CI 1.08-3.95), whereas no risk increase appeared with estrogens supplemented by cyclic or continuous progestins. Mucinous tumors were not associated with hormone replacement therapy. The odds ratio for serous tumors in the highest category of body mass index was 6.47 (95% CI 3.09-13.5). CONCLUSIONS: Increasing parity and lactation reduce the risk of borderline ovarian tumors in women aged 50-74, while no protection follows oral contraceptive use. Hormonal situations such as unopposed estrogen use and obesity, where estrogens are not counteracted by progestins, may increase the risk of serous tumors.     

Does adenocarcinoma of uterine cervix have a worse prognosis than squamous carcinoma?

OBJECTIVE: The objective of this study was to examine the influence of histology on the outcome of patients with cervix carcinoma, treated with radiotherapy and radical surgery. PATIENTS AND METHODS: Clinical, histological, therapeutical and outcome data of 360 patients with stage IB-II cervix carcinoma patients (45 adenocarcinomas and 315 squamous cell carcinoma) managed between 1985 and 1998 were collected from the database of the Institut Gustave-Roussy. RESULTS: The incidence of adenocarcinomas slightly increased during the study period (P =0.07). Histological grade was higher for squamous cell carcinoma than for adenocarcinoma (P =0.08). Adenocarcinomas were smaller than squamous cell carcinoma (P =0.06). With only 38% of sterilized hysterectomy specimen vs 52% for squamous cell carcinomas (P =0.07), adenocarcinoma seemed to be less radiosensitive. With a median follow-up of 67 months, histological type did not influence survival. DISCUSSION AND CONCLUSIONS: Our study demonstrates that radiosensitivity is different between adenocarcinoma and squamous cell carcinoma of the cervix and that surgery may compensate the low radiosensitivity of adenocarcinoma.     

Genetic polymorphisms of FAS and FASL (CD95/CD95L) genes in cervical carcinogenesis: An analysis of haplotype and gene-gene interaction

OBJECTIVE: Whereas human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis, host genetic variations may confer individual susceptibility. Resistance to apoptosis is a hallmark of cancer in which FAS/FAS ligand signaling plays an important role. The present study examines the hypothesis that genetic polymorphisms in FAS and FAS ligand genes, alone or in combination, are associated with cervical carcinogenesis. METHODS: The genotypes of FAS -670A/G, FAS -1377G/A, and FASL -844C/T were assessed in 143 patients with high-grade squamous intraepithelial lesions (HSIL), 175 patients with invasive squamous cell carcinomas (SCC), and in age-matched controls by real-time PCR with allele-specific TaqMan probes. The status of cervical high-risk HPV infection was determined and adjusted to test the independence of genotype in the risk assessment. RESULTS: The A-allele and AA-genotype frequencies of FASA -670G were significantly higher in HSIL/SCC than in controls (60% vs. 54%, P = 0.04, OR 1.26 [95% CI 1.01-1.57]; 38.0% vs. 28.6%, P = 0.02, OR 1.70 [95% CI 1.07-2.70]). No association between FAS -1377 or FASL -844 polymorphisms and HSIL/SCC could be identified. The FAS -1377A/-670A haplotype conferred a higher risk for HSIL/SCC (OR 3.05, 95% CI 1.28-7.30) than FAS -670A alone (OR 1.26, 95% CI 1.28-7.30). The interaction between FAS -670AA and FASL -844CC genotypes was associated with a risk of HSIL/SCC (OR 2.13, 95% CI 1.06-4.29) higher than that of the FAS -670AA genotype alone (OR 1.70, 95% CI 1.07-2.70). CONCLUSIONS: The FAS -1377A/-670A haplotype in combination with FASL -844C is associated with cervical carcinogenesis.     

Prognostic significance of adenocarcinoma histology in women with cervical cancer

Objectives

We performed a population-based analysis to determine the effect of histology on survival for women with invasive cervical cancer.

Methods

The Surveillance, Epidemiology and End Results database was used to identify women with stage IB-IVB cervical cancer treated from 1988 to 2005. Patients were stratified by histology (squamous, adenocarcinoma, and adenosquamous). Clinical characteristics, patterns of care, and outcomes were analyzed using multivariable logistic regression and Cox proportional hazards models.

Results

A total of 24,562 patients were identified including 18,979 (77%) women with squamous cell carcinomas, 4103 (17%) with adencarcinomas, and 1480 (6%) with adenosquamous tumors. Women with adenocarcinomas were younger, more often white, and more frequently married than patients with squamous cell tumors (p < 0.0001 for all). Patients with adenocarcinomas were more likely to present with early-stage disease (p < 0.0001). At diagnosis, 26.7% of women with adenocarcinomas had stage IB1 tumors compared to 16.9% of those with squamous cell carcinomas. Among women with early-stage (IB1-IIA) tumors, patients with adenocarcinomas were 39% (HR = 1.39; 95% CI, 1.23-1.56) more likely to die from their tumors than those with squamous cell carcinomas. For patients with advanced-stage disease (stage IIB-IVA) women with adenocarcinomas were 21% (HR = 1.21; 95% CI, 1.10-1.32) more likely to die from their tumors than those with squamous neoplasms. Five-year survival for stage IIIB neoplasms five-year survival was 31.3% (95% CI, 29.2-33.3%) for squamous tumors vs. 20.3% (95% CI, 14.2-27.1%) for adenocarcinomas.

Conclusion

Cervical adenocarcinomas are more common in younger women and white patients. Adenocarcinoma histology negatively impacts survival for both early and advanced-stage carcinomas.     

Cytoplasmic estrogen receptors in carcinoma of the uterine cervix

The concentration of cytoplasmic estrogen receptors (ER) in cancer of the uterine cervix was measured in 30 cases (28 squamous cell carcinomas and 2 adenocarcinomas). The mean ER concentration in squamous cell carcinoma was 19.3 +/- 26.0 fmol/mg cytosol protein; for pre- and postmenopausal women 6.82 +/- 9.86 and 28.6 +/- 30.1 fmol/mg protein, respectively, were found, the latter being significantly higher. When 'ER-positive' was defined as concentrations greater than 10 fmol/mg protein, 12 of the 28 cases (43%) were found to be ER-positive. There were no significant differences between the ER concentrations of clinical stage I and II squamous cell carcinomas (19.2 +/- 24.2 and 20.9 +/- 27.2 fmol/mg, respectively). ER were detectable in the cervical tissue from all of the control cases of myoma of the uterus. There were, however, no differences in the ER content between the proliferative and secretory phases, but the concentration in premenopausal women was significantly lower than that in postmenopausal women. In comparison with the controls, the mean ER level in both pre- and postmenopausal women with squamous cell carcinoma was significantly lower, due to the fact that ER were not detectable in 57% of these cases. Both cases of cervical adenocarcinoma were ER-positive.     

Postoophorectomy Estrogen Use and Breast Cancer Risk

OBJECTIVE:: To estimate whether the protective effect of premenopausal bilateral oophorectomy on breast cancer risk is mitigated by estrogen therapy use after surgery. METHODS:: In pooled data from four population-based case-control studies spanning 1992-2007, we examined estrogen use after total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) and subsequent breast cancer risk. We identified cases of postmenopausal invasive breast cancer in women (n=10,449) aged 50-79 years from three state tumor registries and age-matched control group participants without breast cancer (n=11,787) from driver's license and Medicare lists. Total abdominal hysterectomy with bilateral salpingo-oophorectomy and estrogen use were queried during structured telephone interviews. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with multivariable logistic regression. RESULTS:: Breast cancer risk comparisons were made relative to women who experienced natural menopause and never used hormones. Overall, breast cancer risk increased 14% among women currently using estrogens after TAHBSO (OR 1.14, 95% CI 1.03-1.28), 32% for estrogen durations less than 10 years (OR 1.32, 95% CI 1.11-1.57), and 22% for estrogen initiation within 5 years of TAHBSO (OR 1.22, 95% CI 1.09-1.37). Among women who underwent early TAHBSO (younger than 40 years), 24-30% decreases in breast cancer risk were observed among both never (OR 0.70, 95% CI 0.55-0.88) and current (OR 0.76, 95% CI 0.61-0.96) estrogen users. CONCLUSION:: Unopposed estrogen use does not negate the reduction in breast cancer risk associated with early (younger than 40 years) bilateral oophorectomy. However, initiating estrogen therapy after TAHBSO at ages 45 and older can increase breast cancer risk and should be considered carefully. LEVEL OF EVIDENCE:: II.     

Multidirectional differentiation of endometrial carcinoma with special reference to tumor aggressiveness evaluated by Ki-67 expression

To clarify the correlation between multidirectional differentiation and aggressiveness of endometrial adenocarcinomas, we assessed both proliferative activities (PA) using Ki-67 expression and squamous and/or endocrine differentiation. We divided 51 adenocarcinomas into 22 adenocarcinomas with typical squamous differentiation (>/=10% of tumor cells, typical SQ) classified into 10 adenoacanthomas (AA) and 12 adenosquamous carcinomas (AS), 17 adenocarcinomas with focal squamous differentiation (<10% of tumor cells), and 12 typical adenocarcinomas without morphological squamous differentiation (pure AC), according to the new WHO classification. Paraffin-embedded sections were stained using monoclonal antibodies against high-molecular-weight keratins (HMWK) to recognize squamous cells, chromogranin A to recognize endocrine cells, and Ki-67 antigen to recognize proliferating cells. Both AA and AS exhibited lower PA than pure AC. Typical SQ exhibited lower PA than pure AC. This difference was also significant after selecting only grade 1 or stage I/II cases. AA exhibited lower PA than AS and also after selecting only grade 1 or stage I/II cases. PA of adenocarcinoma with the expression of HMWK in >/=30% of tumor cells was lower than those without HMWK. PA of adenocarcinoma with the expression of chromogranin A in >/=10% of tumor cells was lower than those without chromogranin A. These differences were also significant after selecting only grade 1 or stage I/II cases. Squamous and/or endocrine differentiation is a good marker for a reduction of PA. Endometrial adenocarcinomas with multidirectional differentiation exhibited lower PA and were likely to be more mature than those with monodirectional differentiation.     

Comparison of human papillomavirus genotypes,sexual, and reproductive risk factors of cervical adenocarcinoma and squamous cell carcinoma: Northeastern United States

OBJECTIVE: Although human papillomavirus causes essentially all cervical carcinoma, cofactors may differ by cancer histologic type. We examined human papillomavirus genotypes and sexual and reproductive risk factors for cervical adenocarcinoma and squamous cell carcinoma. STUDY DESIGN: One hundred twenty-four women with adenocarcinoma, 139 women with squamous cell carcinoma, and 307 control subjects participated in this case-control study. Logistic regression analyses were performed to calculate odds ratios and CIs. RESULTS: Human papillomavirus 18 was associated most strongly with adenocarcinoma (odds ratio, 105; 95% CI, 23-487). Human papillomavirus 16 was associated most strongly with squamous cell carcinoma (odds ratio, 30; 95% CI, 12-77). More than three lifetime sexual partners was a risk factor for adenocarcinoma (odds ratio, 2.1; 95% CI, 1.1-4.0) and squamous cell carcinoma (odds ratio, 3.0; 95% CI, 1.6-5.9). Even being pregnant was associated inversely with adenocarcinoma (odds ratio, 0.4; 95% CI, 0.2-0.8). Five or more pregnancies was associated with squamous cell carcinoma (odds ratio, 2.2; 95% CI, 0.9-5.4). CONCLUSION: The relative importance of human papillomavirus genotypes 16 and 18 and the reproductive co-factor differences suggest distinct causes for cervical adenocarcinoma and squamous cell carcinoma.     

Increase of cervical adenocarcinoma: a report of 520 cases of cervical carcinoma including 112 tumors with glandular elements

A total of 520 new cases of cervical carcinoma were treated at the Department of Obstetrics and Gynecology, Helsinki University Central Hospital, in 1976 through 1980. Of these carcinomas, 95 (18.3%) were pure adenocarcinomas and 17 (3.3%) represented adenosquamous tumors. The mean age was 58.9 years (range 23-88 years). The age distribution was similar in patients with and without malignant glandular elements and the peak incidence was in the age group 60-69 years. In patients with adenocarcinoma, stage I was overrepresented (62.1%) whereas epidermoid carcinomas were more evenly distributed among various stages. The overall 5-year survival rate was 63.1%, with the corresponding corrected rate being 69.1%. The survival rate for patients with adenocarcinoma did not differ significantly from that for patients with squamous cell tumor. It is concluded that in our population the increasing frequency of cervical adenocarcinoma has not influenced the favorable results of the 5-year study. This disease, however, deserves more attention since its etiology, pathogenesis, and biology are still largely unresolved.     

Hormone replacement therapy formulations and risk of epithelial ovarian carcinoma

OBJECTIVE: Hormone replacement therapy (HRT) has been inconsistently linked to ovarian cancer. Estrogen formulations in HRT vary in their effects on estrogen-sensitive target tissues, such as the ovary. The aim of the study is to evaluate the impact of various HRT formulations and their characteristics of use on the risk of epithelial ovarian carcinoma (EOC). METHODS: We assessed the association between the use of HRT and the risk of invasive EOC in women participating in a population-based, case-control study conducted in the Delaware Valley from 1994 to 1998. Cases aged 45 or above at diagnosis (n = 484) were compared to community controls (n = 926) frequency matched by age and area of residence. Information on HRT formulation, timing, and duration were obtained by in-person interview by trained interviewers. HRT formulations were classified as opposed (estrogen + progestin) or unopposed (estrogen alone). They were further categorized according to the estrogen component as either conjugated equine estrogen (CEE), the most common formulation, or non-CEE. Multivariate unconditional logistic regression analyses were used to adjust for age at diagnosis, number of live births, use of oral contraceptives, family history of ovarian carcinoma, and history of tubal ligation. RESULTS: Overall, no association was found between any use of HRT and EOC. Although use of unopposed non-CEE was associated with a significant decrease in risk among hysterectomized women (OR = 0.17, 95% CI = 0.04,0.82), this was not true for women with an intact uterus (OR = 1.14, 95% CI = 0.44,2.98; P for interaction = 0.049). No significant differences in EOC risk were observed for other HRT formulations. CONCLUSIONS: Our results did not suggest any consistent pattern of altered risk for EOC and the overall use of HRT by specific formulations of HRT.