Circulating biomarkers for detection of ovarian cancer and predicting cancer outcomes

Background:

Securing a diagnosis of ovarian cancer and establishing means to predict outcomes to therapeutics remain formidable clinical challenges. Early diagnosis is particularly important since survival rates are markedly improved if tumour is detected early.

Methods:

Comprehensive miRNA profiles were generated on presurgical plasma samples from 42 women with confirmed serous epithelial ovarian cancer, 36 women diagnosed with a benign neoplasm, and 23 comparably age-matched women with no known pelvic mass.

Results:

Twenty-two miRNAs were differentially expressed between healthy controls and the ovarian cancer group (P<0.05), while a six miRNA profile subset distinguished presurgical plasma from benign and ovarian cancer patients. There were also significant differences in miRNA profiles in presurgical plasma from women diagnosed with ovarian cancer who had short overall survival when compared to women with long overall survival (P<0.05).

Conclusion:

Our preliminary data support the utility of circulating plasma miRNAs to distinguish women with ovarian cancer from those with a benign mass and identify women likely to benefit from currently available treatment for serous epithelial ovarian cancer from those who may not.     

Association between diabetes,diabetes treatment and risk of developing endometrial cancer

Background:

A growing body of evidence suggests that diabetes is a risk factor for endometrial cancer incidence. However, most of these studies used case-control study designs and did not adjust for obesity, an established risk factor for endometrial cancer. In addition, few epidemiological studies have examined the association between diabetes treatment and endometrial cancer risk. The objective of this study was to assess the relationships among diabetes, diabetes treatment and endometrial cancer risk in postmenopausal women participating in the Women''s Health Initiative (WHI).

Methods:

A total of 88 107 postmenopausal women aged 50–79 years who were free of cancer and had no hysterectomy at baseline were followed until date of endometrial cancer diagnosis, death, hysterectomy or loss to follow-up, whichever came first. Endometrial cancers were confirmed by central medical record and pathology report review. Multivariate Cox proportional hazards regression models were used to estimate hazard ratios (HRs) (95% confidence interval (CI)) for diagnosis of diabetes and metformin treatment as risk factors for endometrial cancer.

Results:

Over a mean of 11 years of follow-up, 1241 endometrial cancers developed. In the primary analysis that focused on prevalent diabetes at enrolment, compared with women without diabetes, women with self-reported diabetes, and the subset of women with treated diabetes, had significantly higher risk of endometrial cancer without adjusting for BMI (HR=1.44, 95% CI: 1.13–1.85 for diabetes, HR=1.57, 95% CI: 1.19–2.07 for treated diabetes). However after adjusting for BMI, the associations between diabetes, diabetes treatment, diabetes duration and the risk of endometrial cancer became non-significant. Elevated risk was noted when considering combining diabetes diagnosed at baseline and during follow-up as time-dependent exposure (HR=1.31, 95% CI: 1.08–1.59) even after adjusting for BMI. No significant association was observed between metformin use and endometrial cancer risk.

Conclusions:

Our results suggest that the relationship observed in previous research between diabetes and endometrial cancer incidence may be largely confounded by body weight, although some modest independent elevated risk remains.     

Are two-centimeter breast cancers large or small?

Background

Node-negative breast cancers from 2 cm to 5 cm in size are classified as stage ii, and smaller cancers, as stage i. We sought to determine if the prognosis of women with a breast cancer exactly 2 cm in size more closely resembles that of women with a stage i or a stage ii breast cancer.

Methods

Using a cohort of 4265 young women with breast cancer, we compared the 10-year breast cancer mortality rates for women who had a tumour 0.1–1.9 cm, exactly 2.0 cm, and 2.1–2.9 cm.

Results

In the first 3 years after diagnosis, the survival pattern of women with a 2.0-cm breast cancer was nearly identical to that of women with a larger cancer (2.1–3.0 cm). From year 3 to year 10, the relative survival of women with a 2.0-cm breast cancer was improved and nearly identical to that of women with a smaller cancer. The 10-year survival rate was 89.3% for women with tumours less than 20 mm, 86.1% for women with tumours equal to 20 mm, and 81.2% for women with 21-mm to 29-mm tumours.

Conclusions

For young women with small breast cancers, the relative mortality from breast cancer is dynamic with increasing tumour size and varies with time from diagnosis.     

Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis

Background:

An increased lymphoma risk is well documented in systemic lupus (SLE). Less attention has been focused on women''s cancers, even though SLE affects mostly females. Our objective was to estimate the risk of breast, ovarian, and endometrial cancers in SLE, relative to the general population.

Methods:

Data were included from five recent studies of large SLE cohorts. The number of cancers observed was determined for each cancer type. The expected number of malignancies was ascertained from general population data. The parameter of interest was the standardised incidence ratio (SIR), the ratio of observed to expected malignancies.

Results:

The five studies included 47 325 SLE patients (42 171 females) observed for 282 553 patient years. There were 376 breast cancers, 66 endometrial cancers, and 44 ovarian cancers. The total number of cancers observed was less than that expected, with SIRs of 0.76 (95% CI: 0.69, 0.85) for breast cancer, 0.71 (95% CI: 0.55, 0.91) for endometrial cancer, and 0.66 (95% CI: 0.49, 0.90) for ovarian cancer.

Conclusions:

Data strongly support a decreased risk of breast, ovarian, and endometrial cancers in SLE. This may be due to inherent differences in women in SLE (vs the general population) regarding endogenous oestrogen, other medications, and/or genetic make-up.     

Hormone replacement therapy and outcomes for women with non-small-cell lung cancer: can an association be confirmed?

Background

A recent report suggested that women who had been taking hormone replacement therapy (hrt) experienced significantly decreased survival after a lung cancer diagnosis. Given the large cohort of women who have received hrt, it is important to try to confirm that association.

Methods

We reviewed female patients diagnosed with lung cancer at our institution between January 1999 and December 2003 for age at diagnosis, disease stage, treatment, smoking history, hrt, performance status, weight loss, age at menopause, and overall survival. Patients were excluded if they had small-cell lung cancer or an unknown primary cancer, or if they had had previous or synchronous non-lung, non-skin cancers. Statistical analysis used the chi-square test for categorical variables and the Kaplan–Meier method and Cox regression model for univariate and multivariate analyses of overall survival.

Results

Of 397 eligible patients, most (68%) were stage iii or iv. The group included very few never-smokers (5%). The proportion of patients with experience of prior or current hrt was 29%, and no effect on overall survival was observed. Median survival was 13 months in the non-hrt group and 14 months in the hrt group. Significant factors predicting for overall survival included performance status, stage, and weight loss.

Conclusions

Stage, performance status, and weight loss are the most powerful predictors of survival for women with non-small-cell lung cancer. As compared with non-hrt users, patients with prior hrt use did not have inferior outcomes, failing to duplicate previously published results.     

Early detection of ovarian and fallopian tube cancer by examination of cytological samples from the endometrial cavity

Background:

Accumulating evidence suggests that many ovarian high-grade serous carcinomas (HGSCs) originate in the fallopian tube. Malignant cells shed by tubal lesions can be detected by examination of cytological samples from the endometrial cavity (endometrial cytological testing). To evaluate the use of this method for detecting HGSC, we examined epithelial ovarian, fallopian tube, and primary peritoneal cancer patients.

Methods:

Endometrial cytological testing was performed for endometrial cancer screening in asymptomatic women and for pre-treatment evaluation in symptomatic suspected ovarian, tubal, and peritoneal cancer patients.

Results:

Of the 122 ovarian, tubal, and peritoneal cancer patients, malignant cells were identified in 5 patients who did not show detectable abnormalities on imaging studies. Cervicovaginal cytology was positive in only one of these five patients. Four patients were asymptomatic and one was symptomatic. Three asymptomatic patients had early-stage HGSCs, and the other asymptomatic patient had positive peritoneal cytology findings but no detectable tumour. HGSC patients were significantly more likely to have positive findings on endometrial cytology than patients with other histological types (23% vs 6%, P=0.02).

Conclusion:

Endometrial cytological testing can detect early-stage ovarian, tubal, and peritoneal HGSCs without detectable pelvic masses and may be useful for ovarian cancer screening.     

DNA mismatch repair-related protein loss as a prognostic factor in endometrial cancers

Objective

Recent investigations have revealed DNA mismatch repair (MMR) gene mutations are closely related with carcinogenesis of endometrial cancer; however the impact of MMR protein expression on prognosis is not determined. Correlations between MMR-related protein expression and clinicopathological factors of endometrial cancers are analyzed in the present study.

Methods

A total of 191 endometrial cancer tissues treated between 1990 and 2007 in our hospital were enrolled. Immunoreactions for MSH2, MLH1, MSH6, and PMS2 on tissue microarray specimens and clinicopathological features were analyzed retrospectively.

Results

Seventy-six cases (40%) had at least one immunohistochemical alteration in MMR proteins (MMR-deficient group). There were statistically significant differences of histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and histological grade between MMR-deficient group and the other cases (MMR-retained group). Response rate of first-line chemotherapy in evaluable cases was slightly higher in MMR-deficient cases (67% vs. 44%, p=0.34). MMR-deficient cases had significantly better progression-free and overall survival (OS) compared with MMR-retained cases. Multivariate analysis revealed MMR status was an independent prognostic factor for OS in endometrial cancers.

Conclusion

MMR-related proteins expression was identified as an independent prognostic factor for OS, suggesting that MMR was a key biomarker for further investigations of endometrial cancers.     

Does thyroid-stimulating hormone influence the prognosis of patients with endometrial cancer? A multicentre trial

Background:

Thyroid function has been suggested to interfere with tumour biology and prognosis in different cancers. The present study was performed to investigate the impact of pre-therapeutic serum thyroid-stimulating hormone (TSH) levels on the prognosis of patients with endometrial cancer.

Methods:

Pre-therapeutic serum TSH was investigated in 199 patients with endometrial cancer. After stratification in TSH risk groups, univariate and multivariable survival analyses were performed.

Results:

Elevated TSH was independently associated with poor disease-specific survival in univariate/multivariable survival analyses (P=0.01 and P=0.03, respectively).

Conclusion:

Thyroid-stimulating hormone may serve as a novel and independent prognostic parameter for disease-specific survival in patients with endometrial cancer.     

BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers

Background:

Epithelial ovarian cancer is one of the most lethal malignancies, and has a high recurrence rate. Thus, prognostic markers for recurrence are crucial for the care of ovarian cancer. As ovarian cancers frequently exhibit chromosome instability, we aimed at assessing the prognostic significance of two key mitotic kinases, BubR1 and Aurora A.

Methods:

We analysed paraffin-embedded tissue sections from 160 ovarian cancer patients whose clinical outcomes had been tracked after first-line treatment.

Results:

The median recurrence-free survival in patients with a positive and negative expression of BubR1 was 27 and 83 months, respectively (P<0.001). A positive BubR1 expression was also associated with advanced stage, serous histology and high grade. In contrast, Aurora A immunostaining did not correlate with any of the clinical parameters analysed.

Conclusion:

BubR1, but not Aurora A, is a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers.     

Frequency of mutations in mismatch repair genes in a population-based study of women with ovarian cancer

Background:

Mutations in genes for hereditary non-polyposis colorectal cancer (HNPCC) in ovarian cancer patients remains poorly defined. We sought to estimate the frequency and characteristics of HNPCC gene mutations in a population-based sample of women with epithelial ovarian cancer.

Methods:

The analysis included 1893 women with epithelial ovarian cancer ascertained from three population-based studies. Full-germline DNA sequencing of the coding regions was performed on three HNPCC genes, MLH1, MSH2 and MSH6. Collection of demographic, clinical and family history information was attempted in all women.

Results:

Nine clearly pathogenic mutations were identified, including five in MSH6, two each in MLH1 and MSH2. In addition, 28 unique predicted pathogenic missense variants were identified in 55 patients. Pathogenic mutation carriers had an earlier mean age at diagnosis of ovarian cancer, overrepresentation of cancers with non-serous histologies and a higher number of relatives with HNPCC-related cancers.

Conclusions:

Our findings suggest that fewer than 1% of women with ovarian cancer harbour a germline mutation in the HNPCC genes, with overrepresentation of MSH6 mutations. This represents a lower-range estimate due to the large number of predicted pathogenic variants in which pathogenicity could not definitively be determined. Identification of mismatch repair gene mutations has the potential to impact screening and treatment decisions in these women.     

Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients

Background

The risk to develop colorectal and endometrial cancers among subjects testing positive for a pathogenic Lynch syndrome mutation varies, making the risk prediction difficult. Genetic risk modifiers alter the risk conferred by inherited Lynch syndrome mutations, and their identification can improve genetic counseling. We aimed at identifying rare genetic modifiers of the risk of Lynch syndrome endometrial cancer.

Methods

A family based approach was used to assess the presence of genetic risk modifiers among 35 Lynch syndrome mutation carriers having either a poor clinical phenotype (early age of endometrial cancer diagnosis or multiple cancers) or a neutral clinical phenotype. Putative genetic risk modifiers were identified by Next Generation Sequencing among a panel of 154 genes involved in endometrial physiology and carcinogenesis.

Results

A simple pipeline, based on an allele frequency lower than 0.001 and on predicted non-conservative amino-acid substitutions returned 54 variants that were considered putative risk modifiers. The presence of two or more risk modifying variants in women carrying a pathogenic Lynch syndrome mutation was associated with a poor clinical phenotype.

Conclusion

A gene-panel is proposed that comprehends genes that can carry variants with putative modifying effects on the risk of Lynch syndrome endometrial cancer. Validation in further studies is warranted before considering the possible use of this tool in genetic counseling.     

Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia

Objective

The most commonly used classification system for endometrial hyperplasia is the World Health Organization system which is based on subjective criteria. Another classification system is endometrial intraepithelial neoplasia (EIN) system which uses diagnostic criteria including cytological demarcation, crowded gland architecture, minimum size of 1 mm, and careful exclusion of mimics, and aims to identify a precancer or cancer. The objective of this study was to compare the two classification systems in terms of predicting the presence of a coexistent cancer in surgically treated patients.

Methods

Biopsy and hysterectomy specimens of 49 women who were subjected to surgery with a preoperative diagnosis of endometrial hyperplasia (EH) according to the WHO system were re-evaluated retrospectively by using EIN system.

Results

Among the 49 patients, 69.4% had complex atypical EH and 75.5% had EIN at biopsy specimens. EIN was detected in 94.1% of complex atypical EH, and 41.7% of non-atypical EH. Nine women (18.4%) had endometrial cancer. Among women with cancer, all had complex atypical EH or EIN. The rate of coexistent endometrial cancer was 26.5% in women with complex atypical EH and 24.3% in women with EIN.

Conclusion

Diagnoses of atypical or complex atypical EH and EIN had similar sensitivities and negative predictive values in predicting the coexistent endometrial cancer. Either of these two classification systems may be used safely when an experienced pathologist is available. However, use of the objective EIN system may be preferred whenever possible to prevent diagnostic errors in centers where an experienced pathologist is not available.     

Bladder cancer in cancer patients: population-based estimates from a large Swedish study

Background:

This study quantified the risk of urinary bladder neoplasms in cancer patients taking into account the age at first diagnosis, the gender of the patients and the lead time between diagnoses.

Methods:

We used standardised incidence ratios (SIRs) to compare the incidence of bladder tumours in 967 767 cancer patients with the incidence rate in the general Swedish population. A total of 3324 male and 1560 female patients developed bladder tumours at least 1 year after first cancer diagnosis.

Results:

After bladder and renal pelvis cancers, the SIRs of bladder neoplasms were higher in female than in male patients. Men affected by lung, stomach and larynx tumours belonged to the population at high risk for bladder cancer. Treatment of breast, ovarian and cervical cancers seems to contribute to the subsequent development of bladder neoplasms. Long latencies (16–25 years) were observed after testicular, cervical and endometrial cancers. Detection bias had an important role after prostate cancer. Chemotherapy with cyclophosphamide and cisplatin, and also radiotherapy, seem to increase the risk of subsequent neoplasms in the bladder.

Conclusions:

These population-based results may help urologists to assess the risk of bladder neoplasms in cancer survivors. Our data should guide ongoing studies that investigate the effectiveness of bladder cancer screening in cancer patients.     

An epidemiologic risk prediction model for ovarian cancer in Europe: the EPIC study

Background:

Ovarian cancer has a high case-fatality ratio, largely due to late diagnosis. Epidemiologic risk prediction models could help identify women at increased risk who may benefit from targeted prevention measures, such as screening or chemopreventive agents.

Methods:

We built an ovarian cancer risk prediction model with epidemiologic risk factors from 202 206 women in the European Prospective Investigation into Cancer and Nutrition study.

Results:

Older age at menopause, longer duration of hormone replacement therapy, and higher body mass index were included as increasing ovarian cancer risk, whereas unilateral ovariectomy, longer duration of oral contraceptive use, and higher number of full-term pregnancies were decreasing risk. The discriminatory power (overall concordance index) of this model, as examined with five-fold cross-validation, was 0.64 (95% confidence interval (CI): 0.57, 0.70). The ratio of the expected to observed number of ovarian cancer cases occurring in the first 5 years of follow-up was 0.90 (293 out of 324, 95% CI: 0.81–1.01), in general there was no evidence for miscalibration.

Conclusion:

Our ovarian cancer risk model containing only epidemiological data showed modest discriminatory power for a Western European population. Future studies should consider adding informative biomarkers to possibly improve the predictive ability of the model.     

Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer

Background:

The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer.

Methods:

Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed.

Results:

A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1–2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases.

Conclusions:

Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.     

Outcomes of surveillance for contralateral breast cancer in patients less than age 60 at the time of initial diagnosis

Background

After an initial diagnosis of breast cancer, the risk of contralateral breast cancer is approximately 0.5% per year. Annual mammography is recommended to identify local recurrences and contralateral new primaries. Because the sensitivity of mammography tends to be lower in younger women, we conducted a retrospective review of the method of detection and pathologic stage of metachronous contralateral primary breast cancers according to age at diagnosis in a cohort of breast cancer patients.

Methods

The Henrietta Banting Database contains information on cases of breast cancer diagnosed at Women’s College Hospital from 1987 to 2004. From among 1992 women in the database, 71 patients were identified who were initially diagnosed before age 60 and who subsequently developed a contralateral breast cancer. Medical records were obtained for 53 of the 71 patients.

Results

Of the 53 contralateral cancers, 33 (62%) were detected by mammography, including 4 in 16 patients (25%) diagnosed before age 50 and 29 in 37 patients (78%) diagnosed at age 50 or older (p ≤ 0.001).

Conclusions

Mammography has poor sensitivity for the surveillance of contralateral breast cancer in early-onset breast cancer patients. Other imaging modalities should be evaluated in this setting.     

Ovarian cancer mortality among women aged 40-79 years in relation to reproductive factors and body mass index: latest evidence from the Japan Collaborative Cohort study

Objective

This study mainly aimed to investigate the association of ovarian cancer mortality with reproductive factors and body mass index among Japanese women aged 40-79 years.

Methods

The source of the data was the Japan Collaborative Cohort (JACC) study which covered the period of 1988 to 2009. A representative sample of 64,185 women was used. Cox model was used to estimate the relative risk (RR) and 95% confidence interval (CI).

Results

The total number of ovarian cancer deaths was 98, with a mortality rate of 9.30 per 100,000 person-years. Women with single marital status revealed significantly higher age-adjusted RR (RR, 4.11; 95% CI, 1.66 to 10.23; p=0.005) as compared to married women. The effect of single marital status was stronger among older women aged 50+ years (RR, 4.58; 95% CI, 1.65 to 12.72; p=0.003) than younger women. An elevated risk was found for both nulliparous and nullipregnant women. Similarly, an increased risk of ovarian cancer mortality was estimated among overweight among aged 50 years or less.

Conclusion

Out of many factors only single marital status indicated a higher risk for ovarian cancer mortality. All other factors provided inconclusive results, which imply further epidemiological investigations.     

No socioeconomic inequalities in ovarian cancer survival within two randomised clinical trials

Background:

Ovarian cancer is the leading cause of death among cancers of the female genital tract, with poor outcomes despite chemotherapy. There was a persistent socioeconomic gradient in 1-year survival in England and Wales for more than 3 decades (1971–2001). Inequalities in 5-year survival persisted for more than 20 years but have been smaller for women diagnosed around 2000. We explored one possible explanation.

Methods:

We analysed data on 1406 women diagnosed with ovarian cancer during 1991–1998 and recruited to one of two randomised clinical trials. In the second International Collaborative Ovarian Neoplasm (ICON2) trial, women diagnosed between 1991 and 1996 were randomised to receive either the three-drug combination cyclophosphamide, doxorubicin and cisplatin (CAP) or single-agent carboplatin given at optimal dose. In the ICON3 trial, women diagnosed during 1995–1998 were randomised to receive either the same treatments as ICON2, or paclitaxel plus carboplatin.Relative survival at 1, 5 and 10 years was estimated for women in five categories of socioeconomic deprivation. The excess hazard of death over and above background mortality was estimated by fitting multivariable regression models with Poisson error structure and a dedicated link function in a generalised linear model framework, adjusting for the duration of follow-up and the confounding effects of age, Federation of Gynecology and Obstetrics (FIGO) stage and calendar period.

Results:

Unlike women with ovarian cancer in the general population, no statistically significant socioeconomic gradient was seen for women with ovarian cancer treated in the two randomised controlled trials. The deprivation gap in 1-year relative survival in the general population was statistically significant at −6.7% (95% CI (−8.1, −5.3)), compared with −3.6% (95% CI (−10.4, +3.2)) in the trial population.

Conclusions:

Although ovarian cancer survival is significantly lower among poor women than rich women in England and Wales, there was no evidence of an association between socioeconomic deprivation and survival among women with ovarian cancer who were treated and followed up consistently in two well-conducted randomised controlled trials. We conclude that the persistent socioeconomic gradient in survival among women with ovarian cancer, at least for 1-year survival, may be due to differences in access to treatment and standards of care.     

Incidence of cervical,endometrial, and ovarian cancer in Korea, 1999-2010

Objective

To investigate the recent incidence of and trends in cervical, endometrial, and ovarian cancer in Korean females.

Methods

Data from the Korea Central Cancer Registry between 1999 and 2010 were analyzed. Age-standardized rates (ASRs) and annual percent changes (APCs) were calculated.

Results

The absolute incidence rates of the three major gynecologic cancers increased: 6,394 in 1999 to 7,454 in 2010. The ASR for gynecologic cancer was 23.7 per 100,000 in 1999 and decreased to 21.0 in 2010 (APC, -1.1%; 95% confidence interval [CI], -1.53 to -0.70) due to a definitive decrease in the incidence of cervical cancer (APC, -4.3%). Endometrial cancer has been definitively increasing (APC, 6.9% during 1999-2010), especially in females <30 years old (APC, 11.2%) and in females ≥80 years old (APC, 9.5%). The incidence of ovarian cancer is increasing gradually (APC, 1.5%).

Conclusion

ASRs and APC for gynecologic cancers overall are decreasing due to the decrease in the incidence of cervical cancer. However, the incidence of endometrial and ovarian cancer has been increasing.     

Human leukocyte antigen class I expression is an independent prognostic factor in advanced ovarian cancer resistant to first-line platinum chemotherapy

Background:

Loss of HLA class I is important in ovarian cancer prognosis but its role as a prognostic indicator in relation to therapy remains unproven. We studied the prognostic potential of this antigen and its significance in relation to platinum therapy.

Methods:

A total of 157 primary ovarian cancers were assessed for HLA class I immunohistochemically and linked to a comprehensive database of clinicopathological variables, treatment details, and platinum sensitivity.

Results:

Tumours expressing high levels of HLA class I had significantly improved survival (P=0.044). There was a 19-month difference in the median overall survival between tumours with high and low antigen expression. HLA class I antigen expression, stage, and platinum sensitivity were independently predictive of prognosis on multivariate analysis. HLA class I antigen was shown to be expressed at higher levels in patients with good overall survival in platinum-resistant patients (P=0.042). HLA class I significantly correlated with overall survival on multivariate analyses (P=0.034).

Conclusion:

Low-level HLA class I expression is an independent prognostic indicator of poor clinical outcome in ovarian cancer. The survival advantage of patients with platinum-resistant tumours expressing high levels of HLA class I suggests that immunotherapy may be of use in these ovarian cancers resistant to standard chemotherapy.