Summer Dewdney

A Delay from Diagnosis to Treatment Is Associated with a Decreased Overall Survival for Patients with Endometrial Cancer

Objectives While Caucasian women are more likely to be diagnosed with endometrial cancer compared to African-American women, the rate of mortality is higher for African Americans. The cause of this disparity is unknown. We analyzed the time interval from diagnosis of endometrial cancer to treatment as it pertains to race and socioeconomic factors and its possible impact on survival. Methods This was a retrospective, single institution chart review using a cancer registry database. We identified 889 patients who were diagnosed with endometrial cancer between January 2005 and June 2012. Clinicopathologic characteristics, demographics, insurance status, distance from medical center, body mass index (BMI), dates of diagnosis, and treatment were obtained from the medical records. Survival and association was determined by a one-way ANOVA test. Results At the time of the study, 699 patients were alive and 190 dead. The average age was noted to be 62 years (24–91 years). Stages I–IV disease accounted for 69, 6, 15, and 10%, respectively. White race accounted for 64%, African Americans 24%, and Hispanics 7% of our study population. Majority of patients were privately insured (n = 441) followed by Medicare (n = 375). The mean interval time from diagnosis to treatment was 47.5 days (0–363). A statistically significant difference was noted for this time interval with regard to both race and insurance status: white and African Americans (42.6 vs. 57.3 days, p = 0.048), privately insured and Medicare (38.4 vs. 54.1 days, p < 0.001). There was a significant association with increased risk of death with a longer delay (43.3 vs. 64.8 days, p < 0.001). No statistically significance was noted for distance from medical center or BMI. Conclusion A significant increase in interval of time from diagnosis to treatment of endometrial cancer was seen in both race and insurance status. A longer interval from diagnosis to treatment was associated mortality. The causes of these delays are likely multifactorial but deem further investigation given these data.

Immunohistochemical characterization of squamous differentiation and morular metaplasia in uterine endometrioid adenocarcinoma.

Squamous differentiation (SD) and morular metaplasia (MM) are frequently present in uterine endometrioid adenocarcinoma (EAC) and can mimic areas of solid tumor. We used immunohistochemical stains to further characterize these lesions, and to determine which markers would help to distinguish these metaplasias from areas of solid growth in EAC. The pathology database was searched for diagnoses of EAC from 1997 to 2007, the hematoxylin and eosin-stained slides were reviewed, and 143 cases with SD, MM, or both (SD+MM) were identified. A panel of immunohistochemical stains was performed. In particular, we were interested in PAX2 and PAX8, recently studied markers of Müllerian tissue as potential markers for differentiation of metaplasias and tumor. In addition, estrogen receptor and progesterone receptor, and Her-2/neu, were examined to determine whether there was a differential expression between the metaplasias and solid tumor that may be diagnostically useful. In addition, to further characterize MM and SD, bcl-2 as a marker of cell regulation and inhibition of apoptosis, p16 as a surrogate marker for human papillomavirus, and p63 as a marker of mature SD were studied. Adjacent normal endometrium (NEM), when present, and 20 EAC cases (FIGO Grades 1–3) without SD or MM served as controls. PAX2 was positive in NEM (58/61, 95%) and was lost in SD (15/136, 11%), MM (1/25, 4%), and EAC (57/163, 35%), whereas PAX8 was positive in all NEM (61/61, 100%) and in the majority of SD (125/136, 92%), MM (19/25, 73%), and EAC (162/163, 99%). The estrogen receptor and the progesterone receptor were expressed by the majority of EAC (148/163, 91% and 144/163, 88%, respectively), whereas both were markedly diminished in SD (56/136, 41% and 58/136, 43%) and MM (4/25, 16% and 2/25, 8%). Approximately half of the MM was positive for bcl-2 (12/25, 48%), making it an unreliable marker. Her-2/neu was negative in all cases (0%). p16 was patchy in SD (111/136, 82%), MM (22/25, 88%), and EAC (154/163, 94%), whereas p63 was predominantly positive only in SD (96/136, 71%). Estrogen receptor and progesterone receptor, PAX2, and PAX8 were helpful in differentiating MM from SD, EAC, or NEM (P<0.05). In addition, p63 distinguished between SD and MM, supporting the theory that morules do not show characteristic mature SD.

Reducing Overtreatment in Gynecologic Oncology: The Case for Less in Endometrial and Ovarian Cancer

A growing awareness of the harms of overtreatment in cancer care has reached physicians, patients, health policy makers, and medical researchers. Overtreatment exposes patients to the risk of adverse events from procedures or medications that were not necessary. This review examines common practices in gynecologic malignancies that are unlikely to produce direct benefit to patients with these malignancies, but are likely to produce harms. Specifically, we will explore the utility of lymphadenectomy and adjuvant radiation for women with early-stage endometrial cancer; and screening for recurrence and continuous chemotherapy for advanced-stage ovarian cancer patients.

Tumor Screening and DNA Testing in the Diagnosis of Lynch Syndrome

A 43-year-old woman presented with abnormal vaginal bleeding. Endometrial carcinoma was found on dilation and curettage. Hysterectomy and surgical staging confirmed stage IA endometrial cancer. Family history was significant for prostate cancer in her father and paternal grandfather. Her tumor was screened for Lynch syndrome by immunohistochemistry staining for DNA mismatch repair proteins (mutL homolog 1 [MLH1]; MutS homologs 1 and 6 [MSH1, MSH6]; PMS 1 homolog 2 [PMS2]) and microsatellite instability testing (MSI)1 (Table 1).

Society of Gynecologic Oncology Clinical Outcomes Registry: From small beginnings come great things

OBJECTIVE Clinical registries within medical societies have demonstrated the capacity to promote quality improvement. Opportunities for well-designed data repositories could yield reliable national standards for informing reimbursement, determining adherence to care guidelines, maintaining board certification, and developing bundled payment models. Looking to the future, we set out to develop a gynecologic cancer registry serving the members of the Society of Gynecologic Oncology (SGO). METHODS The SGO Clinical Outcomes Registry (COR) initiated a web-based data entry platform as a foray into developing a functional registry, compiling data elements specific to gynecologic oncology. Endometrial and ovarian cancer patients began enrollment in early 2014. Within one year, 19 sites were participating with the addition of cervical cancer patients in January 2015. RESULTS To date, >6500 patients are currently entered from 29 sites, and the COR is being queried to address topics of quality improvement, disparities, and cancer outcomes. CONCLUSIONS The SGO COR has proven the feasibility of developing a functional gynecologic cancer registry, with high uptake, rapid accrual, and ability to investigate topics of quality and outcome using the COR.

Electronic Records, Registries, and the Development of “Big Data”: Crowd-Sourcing Quality toward Knowledge

Despite many perceived advances in treatment over the past few decades, cancer continues to present a significant health burden, particularly to the aging US population. Forces including shrinking funding mechanisms, cost and quality concerns, as well as disappointing clinical outcomes have driven a surge of recent efforts into utilizing the technological innovation that has permeated other industries by leveraging large and complex data sets, so called “big data.” In this review, we will review some of the history of oncology data collection, including the earliest data registries, as well as explore the future directions of this new brand of research while highlighting some of the more recent and promising efforts to harness the power of the electronic health record and the multitude of data co-located there, in an effort to improve individualized cancer-related outcomes in rapid real time.

Endometrial Cancer Surveillance Counterpoint: USA

In the United States, endometrial cancer is the most common malignancy of the female genital tract. It is estimated that 43,470 women were diagnosed with endometrial cancer in 2010 and 7,950 died of their cancer [1]. Fortunately, the majority of endometrial cancers are diagnosed at an early stage due to abnormal uterine bleeding, and most of these women are cured. Approximately 70 % are diagnosed with localized disease, with a corresponding 5-year survival rate of 95 % [1]. Although there has been a decrease in the death rate of endometrial cancer by a small percentage since 1991, there has been an increase in incidence over the past few years [1], likely attributable to the increasing prevalence of obesity. Other risk factors for endometrial cancer include diabetes, hypertension, endogenous or exogenous excess estrogen, nulliparity, family history, and endometrial hyperplasia.

Use of cervical mucus to screen for gynecological malignancies: a pilot study.

High-grade malignancies are the leading cause of death from gynecological tumors. Unfortunately, no efficient screening method is available for these tumors. In this paper we report the results of a pilot study based on the frequency of TP53 mutations in these cancers. Mucus from the cervix of 32 hysterectomy specimens with no grossly visible cervical or serosal involvement were included in this study. TP53 exons 5–9 mutations were screened for mutations using single strand conformation polymorphism (SSCP). Immunostain for p53 protein was performed in all fallopian tubes and in a sample from the tumors that were identified prospectively. A total of 32 cases including 19 malignant, and 13 benign cases were included. P53 immunostain was positive in only 5 cases including 3 high grade malignant tumors and 2 precancerous lesions (serous tubal intraepithelial lesion or p53 signature) in the fallopian tubes. A TP53 mutation band pattern was detected by SSCP in 2/3 and 2/2 cases respectively. Twenty-seven cases were negative for p53 imunostain, 4 of which were positive for TP53 mutation by SSCP including 3 low-grade malignancies. The results of this study provide evidence that DNA from precursor lesions of high grade ovarian, fallopian tube and endometrial carcinomas can be detected in cervical mucus. Further studies using different markers, in preoperative setting and large scale screening studies will determine the utility of using cervical mucus to screen for gynecological malignancies.