Does a BRCA mutation plus tamoxifen equal hysterectomy?
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Antineoplastic Agents, Hormonal↗
Biomedical subjects
Karen H Lu
Publications and source records attributed to Karen H Lu.
The BRK tyrosine kinase is expressed in high-grade serous carcinoma of the ovary.
BACKGROUND: We identified the BRK tyrosine kinase in a PCR-based screen of tyrosine kinases expressed by ovarian tumors. BRK expression is restricted to normal differentiating epithelial cells and its overexpression may play a role in processes related to tumor development and growth. Its expression in normal ovary and ovarian tumors has not previously been described, and is the focus of this study. METHODS: BRK expression levels were determined in 14 normal ovaries and 138 high-grade, late stage serous carcinomas of the ovary by immunohistochemical analysis, and in 19 ovarian cancer cell lines and immortalized ovarian surface epithelium by Western blot analysis. Furthermore, BRK/PTK6 gene copy number was determined in seven primary serous carcinomas by fluorescence in situ hybridization. RESULTS: Immunohistochemical studies indicate that BRK is highly expressed in 97/138 (70%) of high-grade, serous carcinomas of the ovary, but is absent in normal ovarian surface epithelia. BRK is also expressed by 9/19 of ovarian cancer cell lines, but is undetectable in immortalized ovarian surface epithelium. Interestingly, the BRK gene has been mapped to chromosome 20q13.3, a site frequently amplified in ovarian cancers, and associated with poor prognosis. We have determined by fluorescence in situ hybridization (FISH) that BRK is specifically amplified at low levels in 6/7 primary ovarian carcinomas. CONCLUSIONS: The amplification of the BRK gene and overexpression of BRK protein in the majority of high-grade serous carcinomas and ovarian cancer cell lines suggest that BRK may play a role in the development and growth of ovarian tumors.
Cell Line, Tumor↗
Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review.
CONTEXT: About 2% of all colorectal cancer occurs in the context of the autosomal dominantly inherited Lynch syndrome, which is due to mutations in mismatch repair genes. Potential risk-reducing interventions are recommended for individuals known to have these mutations. OBJECTIVES: To review cancer risks and data on screening efficacy in the context of Lynch syndrome (hereditary nonpolyposis colorectal cancer) and to provide recommendations for clinical management for affected families, based on available evidence and expert opinion. DATA SOURCES AND STUDY SELECTION: A systematic literature search using PubMed and the Cochrane Database of Systematic Reviews, reference list review of retrieved articles, manual searches of relevant articles, and direct communication with other researchers in the field. Search terms included hereditary non-polyposis colon cancer, Lynch syndrome, microsatellite instability, mismatch repair genes, and terms related to the biology of Lynch syndrome. Only peer-reviewed, full-text, English-language articles concerning human subjects published between January 1, 1996, and February 2006 were included. The US Preventive Services Task Force's 2-tier system was adapted to describe the quality of evidence and to assign strength to the recommendations for each guideline. EVIDENCE SYNTHESIS: The evidence supports colonoscopic surveillance for individuals with Lynch syndrome, although the optimal age at initiation and frequency of examinations is unresolved. Colonoscopy is recommended every 1 to 2 years starting at ages 20 to 25 years (age 30 years for those with MSH6 mutations), or 10 years younger than the youngest age of the person diagnosed in the family. While fully acknowledging absence of demonstrated efficacy, the following are also recommended annually: endometrial sampling and transvaginal ultrasound of the uterus and ovaries (ages 30-35 years); urinalysis with cytology (ages 25-35 years); history, examination, review of systems, education and genetic counseling regarding Lynch syndrome (age 21 years). Regular colonoscopy was favored for at-risk persons without colorectal neoplasia. For individuals who will undergo surgical resection of a colon cancer, subtotal colectomy is favored. Evidence supports the efficacy of prophylactic hysterectomy and oophorectomy. CONCLUSIONS: The past 10 years have seen major advances in the understanding of Lynch syndrome. Current recommendations regarding cancer screening and prevention require careful consultation between clinicians, clinical cancer genetic services, and well-informed patients.
Adult↗
Women with HNPCC: a target population for the chemoprevention of gynecologic cancers.
Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is an autosomal-dominant inherited cancer susceptibility syndrome that is associated with increased risk of development of endometrial and ovarian cancers. Therefore, women with HNPCC are candidates for chemoprevention of gynecological cancers. Although there have been a number of clinical trials examining chemoprevention strategies for colorectal cancer in HNPCC, the information regarding gynecological cancers in HNPCC remains limited. The purpose of this review is to provide an analytical background about the current knowledge regarding gynecological cancers in patients with HNPCC.
Chemoprevention↗
Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer--a plan to move forward.
This article reviews progress in chemopreventive drug development, especially data and concepts that are new since the 2002 AACR report on treatment and prevention of intraepithelial neoplasia. Molecular biomarker expressions involved in mechanisms of carcinogenesis and genetic progression models of intraepithelial neoplasia are discussed and analyzed for how they can inform mechanism-based, molecularly targeted drug development as well as risk stratification, cohort selection, and end-point selection for clinical trials. We outline the concept of augmenting the risk, mechanistic, and disease data from histopathologic intraepithelial neoplasia assessments with molecular biomarker data. Updates of work in 10 clinical target organ sites include new data on molecular progression, significant completed trials, new agents of interest, and promising directions for future clinical studies. This overview concludes with strategies for accelerating chemopreventive drug development, such as integrating the best science into chemopreventive strategies and regulatory policy, providing incentives for industry to accelerate preventive drugs, fostering multisector cooperation in sharing clinical samples and data, and creating public-private partnerships to foster new regulatory policies and public education.
Biomarkers, Tumor↗
Association between adiponectin, insulin resistance, and endometrial cancer.
BACKGROUND: Obesity is a well known risk factor for the development of endometrial cancer; however, weight alone does not account for all cases. The authors hypothesized that insulin resistance also contributes to an increased risk for endometrial cancer. Adiponectin is a protein secreted by adipose cells and has been shown to be a surrogate marker for insulin resistance, with low levels of adiponectin correlated with hyperinsulinemia and degree of insulin resistance. The purpose of the current study was to determine whether there was an independent association between adiponectin level and endometrial cancer. METHODS: A case-control study was performed on 117 endometrial cancer patients (cases) and 238 women with no history of cancer (controls). Serum adiponectin levels were measured using enzyme-linked immunoadsorbent assay and examined for their association with endometrial cancer. Univariate and multivariate logistic regression analyses were performed with adjustment for confounding factors. RESULTS: The mean serum adiponectin levels were significantly lower among cases (88.8+/-63.3 ng/mL) than among controls (148.2+/-68.3; P<.001). This inverse correlation continued to be observed after controlling for age, body mass index, diabetes, and hypertension. Cases were significantly more likely to have serum adiponectin levels in the lowest (odds ratio [OR] of 10.5; 95% confidence interval [95% CI], 4.49-24.57 [P<.001]) and intermediate tertiles (OR of 2.5; 95% CI, 1.01-6.21 [P=.05]) when compared with controls. CONCLUSIONS: Adiponectin level was found to be independently and inversely associated with endometrial cancer. Women with endometrial cancer were more likely to have low adiponectin levels than controls, even after adjusting for body mass index. This suggested that insulin resistance is independently associated with endometrial cancer.
Adiponectin↗
Are women ready for the HPV vaccine?
OBJECTIVE: An HPV (human papillomavirus) vaccine will be available soon. Because vaccination for both boys and girls will be critical to reduce the incidence of this disease, we evaluated the willingness of women to accept the HPV vaccine and to consent to having their children vaccinated. METHODS: A 20-item questionnaire was distributed to women who had children between the ages of 8 and 14 years, the likely age range of the children who will be targeted to receive the vaccine. RESULTS: 200 women completed surveys. The median age for the respondents was 34.4 years (range, 23-53 years). 77% of the women surveyed would be willing to accept an HPV vaccine for themselves. 67% who had a daughter (n = 156) and 66% who had a son (n = 137) would consent to have their child vaccinated. Those not accepting the vaccine cited the risk of unknown adverse effects or their current lack of sexual activity. Women who would not consent to have their children vaccinated cited the risk of unknown adverse effects and their belief that their children are not sexually active. Male children not directly benefiting from the vaccine were also a reason for not considering the vaccine for sons. A history of an abnormal Papanicolaou smear was not associated with willingness to accept the vaccine. CONCLUSIONS: This pilot study demonstrated a willingness of women to accept the HPV vaccine for themselves and their children. Gynecologists and gynecologic oncologists must focus not only on the diagnosis and treatment of cervical cancer but also on its prevention.
Adolescent↗
Lysophosphatidic acid is a major regulator of growth-regulated oncogene alpha in ovarian cancer.
Growth-regulated oncogene alpha (GROalpha), a member of the chemokine superfamily, is commonly expressed in transformed cells and contributes to angiogenesis and tumorigenesis. Here, we report that increased GROalpha levels are detected in the plasma and ascites of ovarian cancer patients. Ovarian cancer cell lines in culture express and secrete GROalpha. However, when they are starved in serum-free medium, ovarian cancer cells ceased producing GROalpha, suggesting that GROalpha is not constitutively expressed but rather is produced in response to exogenous growth factors in ovarian cancer cells. The prototype peptide growth factors present in serum such as platelet-derived growth factor, insulin-like growth factor I, and insulin do not stimulate GROalpha production by ovarian cancer cells. In contrast, lysophosphatidic acid (LPA), a glycerol backbone phospholipid mediator present in serum and ascites of ovarian cancer patients, is a potent inducer of GROalpha expression in ovarian cancer cell lines. Treatment of ovarian cancer cells with LPA leads to transcriptional activation of the GROalpha gene promoter and robust accumulation of GROalpha protein in culture supernatants. The action of LPA on GROalpha expression is mediated by LPA receptors, particularly the LPA(2) receptor in that ectopic expression of these receptors restores the LPA-dependent GROalpha production in nonresponsive cells. Down-regulation of LPA(2) expression by small interfering RNA (siRNA) in ovarian cancer cells desensitizes GROalpha production in response to LPA. The effect of serum on GROalpha production is also significantly decreased by siRNA inhibition of LPA(2) expression. These studies identify LPA as a primary regulator of GROalpha expression in ovarian cancer.
Ascites↗
Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome.
BACKGROUND: Women with the Lynch syndrome (hereditary nonpolyposis colorectal cancer) have a 40 to 60 percent lifetime risk of endometrial cancer and a 10 to 12 percent lifetime risk of ovarian cancer. The benefit of prophylactic gynecologic surgery for women with this syndrome has been uncertain. We designed this study to determine the reduction in the risk of gynecologic cancers associated with prophylactic hysterectomy and bilateral salpingo-oophorectomy in women with the Lynch syndrome. METHODS: Three hundred fifteen women with documented germ-line mutations associated with the Lynch syndrome were identified. Women who had undergone prophylactic hysterectomy (61 women) and women who had undergone prophylactic bilateral salpingo-oophorectomy (47 women) were matched with mutation-positive women who had not undergone the procedure in question (210 women for the analysis of endometrial cancer and 223 for the analysis of ovarian cancer). Women who had undergone prophylactic surgery and their matched controls were followed from the date of the surgery until the occurrence of cancer or until the data were censored at the time of the last follow-up visit. RESULTS: There were no occurrences of endometrial, ovarian, or primary peritoneal cancer among the women who had undergone prophylactic surgery. Endometrial cancer was diagnosed in 69 women in the control group (33 percent), for an incidence density of 0.045 per woman-year, yielding a prevented fraction (the proportion of potential new cancers prevented) of 100 percent (95 percent confidence interval, 90 to 100 percent). Ovarian cancer was diagnosed in 12 women in the control group (5 percent), for an incidence density of 0.005 per woman-year, yielding a prevented fraction of 100 percent (95 percent confidence interval, -62 to 100 percent). CONCLUSIONS: These findings suggest that prophylactic hysterectomy with bilateral salpingo-oophorectomy is an effective strategy for preventing endometrial and ovarian cancer in women with the Lynch syndrome.
Adult↗
Pathologic features of endometrial carcinoma associated with HNPCC: a comparison with sporadic endometrial carcinoma.
BACKGROUND: Endometrial carcinoma is a common malignancy in hereditary nonpolyposis colorectal carcinoma (HNPCC). Like colon carcinoma, endometrial carcinoma is diagnosed at an earlier age in women with HNPCC. In contrast to colon carcinoma, the pathologic features of endometrial carcinoma in HNPCC have not been studied in detail. It was the purpose of this study to pathologically characterize a series of HNPCC associated endometrial carcinomas. METHODS: Fifty women with HNPCC and endometrial carcinoma were analyzed from four different hereditary cancer registries. H&E stained slides and pathology reports were reviewed for clinically important pathologic features of endometrial carcinoma. These results were compared with those for two different groups of sporadic endometrial carcinoma--women younger than age 50 years (n = 42) and women of all ages with tumors demonstrating microsatellite instability (MSI-high) secondary to methylation of MLH1 (n = 26). RESULTS: Nearly one-fourth of HNPCC patients in this study had endometrial tumors with pathologic features that would require adjuvant therapy after hysterectomy. There was a trend toward the HNPCC patients having more nonendometrioid tumors; all of these patients were carriers of MSH2 mutations. Such nonendometrioid tumors were extremely rare in the MLH1 methylated group. A subset of MLH1 methylated sporadic tumors demonstrated a unique, 'undifferentiated' histology that was not observed in HNPCC or the young group. CONCLUSION: Data suggest a genotype-phenotype relation in which microsatellite instability resulting from MLH1 methylation is almost exclusively associated with classical or 'undifferentiated' endometrioid tumors, whereas microsatellite instability secondary to MSH2 mutation can result in a more variable histologic spectrum of endometrial carcinoma.
Adaptor Proteins, Signal Transducing↗
Clinical behavior of stage II-IV low-grade serous carcinoma of the ovary.
OBJECTIVE: To analyze the clinical behavior of patients with stage II-IV low-grade serous carcinoma of the ovary seen at our institution who underwent primary surgery followed by platinum-based chemotherapy. METHODS: Patients with stage II-IV low-grade serous carcinoma of the ovary from 1978 to 2003 were identified using existing databases. Clinicopathologic information was obtained from medical records. Progression-free survival and overall survival were estimated by the method of Kaplan and Meier. The log-rank test was used to compare differences between survival curves. Univariable and multivariable analyses were performed using Cox proportional hazards regression. RESULTS: We identified 112 eligible patients. Median age was 43 years.; 90% had stage III disease. Preoperative serum CA 125 was elevated in 86% of patients. The most common sites of extraovarian disease were omentum, fallopian tubes, pelvic peritoneum, and uterus. Response rate to platinum-based chemotherapy in 10 evaluable patients (15% of patients with gross residual disease) was 80%, and 42 patients underwent second-look surgery: microscopically negative findings, 2 (5%); microscopically positive disease, 13 (33%); macroscopically positive disease, 24 (62%); and insufficient information, 3 (7%). Median progression-free survival and overall survival times were 19.5 and 81.8 months. Persistent disease after primary chemotherapy was the only factor associated with shorter overall survival time (hazard ratio 3.46, 95% confidence interval 2.00-5.97, P<.001). CONCLUSION: Metastatic low-grade serous carcinoma of the ovary is characterized by young age at diagnosis and prolonged overall survival. Segregating women with this diagnosis in future clinical trials is warranted.
Adolescent↗
Prophylactic bilateral salpingo-oophorectomy compared with surveillance in women with BRCA mutations.
OBJECTIVE: The objective of this study was to evaluate clinical factors associated with choosing prophylactic bilateral salpingo-oophorectomy (BSO) over surveillance in women with a BRCA1 or BRCA2 mutation. METHODS: Between 1996 and 2005, 139 women who tested positive for a BRCA1 or BRCA2 mutation were identified. Thirty-three women were excluded due to a personal history of ovarian or fallopian tube cancer before genetic testing, resulting in 106 women for the final analysis. The characteristics of women who underwent prophylactic BSO were compared with those choosing surveillance. RESULTS: Sixty-five of the BRCA mutation carriers (61%) underwent prophylactic BSO. Median age at BSO was 45.6 years. Median time from disclosure of genetic test results to surgery was 4.6 months. Eighty-five percent of women who underwent prophylactic BSO were parous compared with 66% of women who chose surveillance (P = .03). A previous diagnosis of breast cancer was noted in 72% of women who underwent prophylactic BSO compared with 46% of women undergoing surveillance (P < .01). Fifty-two women (80%) had hysterectomy performed at the time of BSO. Two women had incidental ovarian cancer diagnosed at time of surgery. CONCLUSION: Age greater than 40 years, parity, and a personal history of breast cancer were associated with choosing prophylactic BSO in our cohort. A short time interval was noted from the time of receiving positive genetic test results to undergoing prophylactic surgery.
Adult↗
Women with synchronous primary cancers of the endometrium and ovary: do they have Lynch syndrome?
PURPOSE: Lynch syndrome (hereditary nonpolyposis colorectal cancer; HNPCC) is an autosomal-dominant cancer predisposition syndrome that increases risk for multiple cancers, including colon, endometrial, and ovarian cancer. Revised Bethesda Criteria recommend that patients with two HNPCC-associated cancers undergo molecular evaluation to determine whether they have a mismatch repair (MMR) defect associated with HNPCC. The purpose of our study was to determine the likelihood of MMR defects (MSH2, MSH6, MLH1) in women with synchronous endometrial and ovarian cancer. PATIENTS AND METHODS: Between 1989 and 2004, 102 women with synchronous endometrial and ovarian cancers were identified; 59 patients had tumor blocks available for analysis. Patients were divided into risk groups based on family history: high (met Amsterdam criteria), medium (personal history or first-degree relative with an HNPCC-associated cancer), and low (all others). Protein expression for MSH2, MSH6, and MLH1 was evaluated by immunohistochemistry. Microsatellite instability and MLH1 promoter methylation analyses were performed on a subset of cases. RESULTS: Median age was 50 years. Two patients met Amsterdam criteria for HNPCC. Five additional patients, all medium-risk, had molecular findings consistent with a germline mutation of either MSH2 or MLH1. None of the low-risk patients had molecular results consistent with a germline mutation. CONCLUSION: Overall, 7% of women in our cohort met either clinical or molecular criteria for Lynch syndrome. All of these women had a prior history or a first-degree relative with an HNPCC-associated cancer. Limiting genetic evaluation to women with synchronous endometrial and ovarian cancer who have a family history suggestive of HNPCC may appropriately identify women with Lynch syndrome.
Adult↗
Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary.
Papillary serous low malignant potential (LMP) tumors are characterized by malignant features and metastatic potential yet display a benign clinical course. The role of LMP tumors in the development of invasive epithelial cancer of the ovary is not clearly defined. The aim of this study is to determine the relationships among LMP tumors and invasive ovarian cancers and identify genes contributing to their phenotypes. Affymetrix U133 Plus 2.0 microarrays (Santa Clara, CA) were used to interrogate 80 microdissected serous LMP tumors and invasive ovarian malignancies along with 10 ovarian surface epithelium (OSE) brushings. Gene expression profiles for each tumor class were used to complete unsupervised hierarchical clustering analyses and identify differentially expressed genes contributing to these associations. Unsupervised hierarchical clustering analysis revealed a distinct separation between clusters containing borderline and high-grade lesions. The majority of low-grade tumors clustered with LMP tumors. Comparing OSE with high-grade and LMP expression profiles revealed enhanced expression of genes linked to cell proliferation, chromosomal instability, and epigenetic silencing in high-grade cancers, whereas LMP tumors displayed activated p53 signaling. The expression profiles of LMP, low-grade, and high-grade papillary serous ovarian carcinomas suggest that LMP tumors are distinct from high-grade cancers; however, they are remarkably similar to low-grade cancers. Prominent expression of p53 pathway members may play an important role in the LMP tumor phenotype.
Carcinoma, Papillary↗
Patterns of gene expression in different histotypes of epithelial ovarian cancer correlate with those in normal fallopian tube, endometrium, and colon.
PURPOSE: Epithelial ovarian cancers are thought to arise from flattened epithelial cells that cover the ovarian surface or that line inclusion cysts. During malignant transformation, different histotypes arise that resemble epithelial cells from normal fallopian tube, endometrium, and intestine. This study compares gene expression in serous, endometrioid, clear cell, and mucinous ovarian cancers with that in the normal tissues that they resemble. EXPERIMENTAL DESIGN: Expression of 63,000 probe sets was measured in 50 ovarian cancers, in 5 pools of normal ovarian epithelial brushings, and in mucosal scrapings from 4 normal fallopian tube, 5 endometrium, and 4 colon specimens. Using rank-sum analysis, genes whose expressions best differentiated the ovarian cancer histotypes and normal ovarian epithelium were used to determine whether a correlation based on gene expression existed between ovarian cancer histotypes and the normal tissues they resemble. RESULTS: When compared with normal ovarian epithelial brushings, alterations in serous tumors correlated with those in normal fallopian tube (P = 0.0042) but not in other normal tissues. Similarly, mucinous cancers correlated with those in normal colonic mucosa (P = 0.0003), and both endometrioid and clear cell histotypes correlated with changes in normal endometrium (P = 0.0172 and 0.0002, respectively). Mucinous cancers displayed the greatest number of alterations in gene expression when compared with normal ovarian epithelial cells. CONCLUSION: Studies at a molecular level show distinct expression profiles of different histologies of ovarian cancer and support the long-held belief that histotypes of ovarian cancers come to resemble normal fallopian tube, endometrial, and colonic epithelium. Several potential molecular markers for mucinous ovarian cancers have been identified.
Adenocarcinoma, Clear Cell↗
Atypical PKCiota contributes to poor prognosis through loss of apical-basal polarity and cyclin E overexpression in ovarian cancer.
We show that atypical PKCiota, which plays a critical role in the establishment and maintenance of epithelial cell polarity, is genomically amplified and overexpressed in serous epithelial ovarian cancers. Furthermore, PKCiota protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKCiota DNA copy number is associated with decreased progression-free survival in serous epithelial ovarian cancers. In a Drosophila in vivo epithelial tissue model, overexpression of persistently active atypical PKC results in defects in apical-basal polarity, increased Cyclin E protein expression, and increased proliferation. Similar to the Drosophila model, increased PKCiota proteins levels are associated with increased Cyclin E protein expression and proliferation in ovarian cancers. In nonserous ovarian cancers, increased PKCiota protein levels, particularly in the presence of Cyclin E, are associated with markedly decreased overall survival. These results implicate PKCiota as a potential oncogene in ovarian cancer regulating epithelial cell polarity and proliferation and suggest that PKCiota is a novel target for therapy.
Animals↗
Potential markers that complement expression of CA125 in epithelial ovarian cancer.
BACKGROUND: When ovarian carcinoma is diagnosed in stage I, up to 90% of patients can be cured with surgery and currently available chemotherapy. At present, less than 25% of cases are diagnosed at this stage. To increase the fraction of ovarian cancers detected at an early stage, screening strategies have been devised that utilize a rising serum CA125 level to trigger the performance of transvaginal sonography. One limitation of CA125 as an initial step in such a screening strategy is that up to 20% of ovarian cancers lack expression of the antigen. Serum tumor markers that can be detected in ovarian cancers that lack CA125 expression might improve the sensitivity for early detection. METHODS: From 296 ovarian cancers, 65 (22%) were found to have weak or absent CA125 expression on immunoperoxidase staining. Tissue expression of CA125 was compared to serum CA125 levels. Using immunoperoxidase staining of tissue arrays, we have assessed expression of 10 potential serum tumor markers in the 65 epithelial ovarian cancers with little or no CA125 expression and in ovarian cystadenomas, tumors of low malignant potential, normal ovaries, and 16 other normal tissues. RESULTS: Low or absent expression of CA125 in surgical specimens of epithelial ovarian cancer was associated with low levels of serum CA125 in pre-operative serum specimens. In ovarian cancers that lacked CA125, all specimens (100%) expressed human kallikrein 10 (HK10), human kallikrein 6 (HK6), osteopontin (OPN), and claudin 3. A smaller fraction of CA125-deficient ovarian cancers expressed DF3 (95%), vascular endothelial growth factor (VEGF) (81%), MUC1 (62%), mesothelin (MES) (34%), HE4 (32%), and CA19-9 (29%). When reactivity with normal tissues was considered, however, MES and HE4 showed the greatest specificity. Differential expression was also found for HK10, OPN, DF3, and MUC1. CONCLUSIONS: At the level of tissue expression, each of 10 potential serum markers could be detected in 29-100% of ovarian cancers that had low or absent expression of CA125. Several markers exhibited more intense expression in cancers than in normal organs. Further investigation is needed to demonstrate complementary expression of markers in serum.
Antigens↗
Endometrial cancer in young, normal-weight women.
OBJECTIVE: To determine if young, normal-weight women with endometrial cancer have unique risk factors and clinical characteristics when compared with young, overweight and obese women with endometrial cancer. METHODS: Between 1989 and 2003, 1531 patients were treated for endometrial cancer. 188 (12%) of these women were premenopausal and under the age of 50 at time of diagnosis. The patients were divided into three groups based on body mass index (BMI): normal weight (BMI < 25 kg/m2), overweight (BMI 25-30 kg/m2) and obese (BMI > or = 30 kg/m2). Clinical and pathologic characteristics were compared. RESULTS: Of the 188 young endometrial cancer patients, 47 (25%) were of normal weight, 31 (17%) overweight and 106 (56%) obese. 4% of normal-weight, 12% of overweight and 0% of obese patients met criteria for Lynch syndrome/hereditary non-polyposis colorectal cancer (HNPCC). Irregular menstrual cycles were reported by 30% normal-weight, 32% of overweight and 61% of obese women (P = 0.001). 17% of normal-weight, 7% of overweight and 14% of obese women had a history of infertility (P = 0.723). Nulliparity was noted in 57% of normal-weight, 47% of overweight and 57% of obese patients (P = 0.583). Diabetes was reported in 4% of normal-weight, 13% of overweight and 35% of obese patients (P < 0.001). 28% of normal-weight, 26% of overweight and 14% of obese patients had synchronous primary tumors of the endometrium and ovary. CONCLUSIONS: As expected, a significantly higher proportion of obese and overweight women had diabetes and irregular menstrual cycles. Among the normal-weight women, a high proportion were nulliparous, had a history of infertility, irregular menstrual cycles and synchronous tumors of the endometrium and ovary when compared with the general population. This suggests that hormonal factors, and possibly polycystic ovarian syndrome (PCOS), may contribute to the development of endometrial cancer in young normal-weight women.
Adult↗