Grainger S. Lanneau

Human Tumor Antigens Tn and Sialyl Tn Arise from Mutations in Cosmc

Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase. Diverse neoplastic lesions, including colon cancer and melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of-function mutations in Cosmc. In addition, two human cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the first example of somatic mutations in multiple types of cancers that cause global alterations in cell surface carbohydrate antigen expression.

Vulvar cancer in young women: demographic features and outcome evaluation.

OBJECTIVE The objective of the study was to identify prognostic and environmental factors associated with vulvar carcinoma in young women. STUDY DESIGN This study was a review of patients younger than 45 years who were diagnosed with vulvar squamous cell carcinoma between 1994 and 2006. RESULTS Fifty-six patients were identified. Median age was 38 years and median follow-up was 25.3 months. Fifty-eight percent of patients presented with stage I disease; 77% smoked tobacco. Of patients with advanced disease, 53.3% were smokers, 40% had human papillomavirus (HPV) exposure, 46.7% had a history of vulvar intraepithelial neoplasia (VIN), and 6.7% were immunocompromised. Symptoms were present for more than 12 months in 47%, but symptom duration did not correlate with stage (P = .42) or positive lymph nodes (P = .28). Disease recurred in 10.7% and 5.4% died of disease. CONCLUSION Young women with vulvar cancer tend to have early-stage disease, smoke, have a history of HPV, and have VIN. Many of the factors that place these patients at continuous risk are modifiable.

Stage IVB endometrial cancer: Does applying an ovarian cancer treatment paradigm result in similar outcomes? A case-control analysis

OBJECTIVE The pattern of metastasis for Stage IV endometrial carcinoma (EC) is similar to that for ovarian carcinoma (OC), hence the goal of surgical management for both diseases is optimal cytoreduction (CRS) followed by adjuvant chemotherapy. The objective of this study is to evaluate overall survival (OS) and progression-free survival (PFS) in patients with advanced EC compared to a cohort of patients with OC matched for age and residual disease. METHODS Patients with Stage IVB EC treated with curative intent between the years of 1990-2006 were identified and data abstracted regarding demographics, surgical procedures, pathologic factors, and follow-up. Two patients with Stage IIIC OC were matched for each Stage IVB EC based on age and residual disease. Stage IVB EC patients with distant metastasis were excluded. All OC patients underwent primary CRS and received combination platinum based chemotherapy. PFS and OS were evaluated using Kaplan-Meier curves and log-rank analysis. RESULTS 55 patients with Stage IVB EC underwent primary CRS and adjuvant therapy with curative intent. Optimal CRS (<1 cm residual disease) was achieved in 87% (n=48). The most common histologic subtypes were serous (53%, n=29), endometrioid (44%, n=24) and clear cell (3%, n=2). Adjuvant therapy with curative intent included platinum based combination chemotherapy (60%, n=33), platinum based chemotherapy with radiation (25%, n=14), and radiation alone (15%, n=8) depending on the time period of treatment. Seven patients had residual disease >1 cm following CRS, 6 of whom received chemotherapy alone. Two-year OS for the entire cohort was 52 vs. 76% for patients with EC compared to OC (p=0.008). For suboptimal EC vs. OC patients was 33% vs. 66% for OC patients (p=NS). EC patients with optimal CRS had OS of 57% at 2 years compared to 82% for OC patients (p=0.02). Median PFS was 13 months vs. 20 months for all EC and OC patients, respectively (p=0.01). Using a Cox proportional hazards model, optimal CRS was associated with a survival advantage over suboptimal for EC patients with a hazard ratio of 2.4. CONCLUSIONS The treatment paradigm for advanced EC has undergone a drastic evolution from palliation to CRS and combination chemotherapy. Despite similarities in disease distribution and histology, OS for EC patients with intraperitoneal metastasis does not approach that of patients with advanced OC. Further research to identify the molecular characteristics of EC may identify important differences from OC and provide insight for the development of novel primary and salvage treatment strategies for patients with advanced EC.

Tubal Ligation Frequency in Oklahoma Women with Cervical Cancer

OBJECTIVE Infrequent Pap screening is an important risk factor for cervical cancer. We studied the association between contraceptive methods, screening frequency, and cancer. METHODS Women (n=2004) enrolled in the cross-sectional Study to Understand Cervical Cancer Endpoints and Determinants (SUCCEED) underwent colposcopy to evaluate an abnormal Pap test. Questionnaire data were compared between those with cervical intraepithelial neoplasia (CIN) 3/adenocarcinoma in situ (AIS) and those with invasive cancer to identify factors associated with cancer. Logistic regression was used to calculate age-stratified measures of association between contraceptive method and Pap frequency as well as tubal ligation (TL) and cancer risk. RESULTS In all age groups, women with TL were more likely to have had no Pap screening in the previous 5 years compared to women using other contraception: 26-35 years (OR 4.6, 95% CI 2.4-8.6; p<0.001), 36-45 years (OR 3.8, 95% CI 2.1-7.0; p<0.001), and 46-55 years (OR 2.2, 95% CI 1.0-4.9; p=0.050). Subjects with cancer (n=163) were more likely to have had a TL (41% vs. 21%, p<0.001) than those with CIN 3/AIS (n=370). Age-stratified analyses showed increased odds of tubal ligation in women with cancer versus those with CIN 3/AIS between 25 and 45 years, with a significant increase in women 26 to 35 years old (OR 3.3, 95% CI 1.4-8.1; p=0.009). Adjusting for Pap frequency changed the effect only slightly, suggesting that increased risk was not fully mediated by lack of screening. CONCLUSION Contraceptive type is associated with Pap screening. Women with TLs obtain less frequent Pap testing and may be at an increased risk for cervical cancer.

A LEEP cervical conization is rarely indicated for a two-step discrepancy.

Objectives. The current indications for conization of the cervix include a 2-step discrepancy between cervical cytological and histological findings. We sought to determine the utility of a loop electrocautery excision procedure (LEEP) cone for a 2-step discrepancy. Methods. A retrospective institutional review board-approved chart review was performed on all women recommended to undergo a LEEP secondary to a discrepancy between a referral high-grade squamous intraepithelial lesion cytological finding and a subsequent colposcopic biopsy result revealing either normal or cervical intraepithelial neoplasia (CIN) 1 histological finding; CIN 2 was excluded from the study. Statistical analysis was performed using SAS 9 (SAS Institute, Inc, Cary, NC). The results were considered significant if a p value less than or equal to.05 was demonstrated. Results. Fifty-nine patients received a LEEP for a 2-step discrepancy between cytological and histological findings. Twenty-seven patients had a second pass or LEEP cone. Among the patients with a normal cervical biopsy result and a high-grade cytological finding, 10 (29%) of 34 had normal histological findings, as revealed by LEEP, and 14 (41%) of 34 had CIN 3; 16 (64%) of 25 patients with high-grade cytological finding and CIN 1 biopsy finding had CIN 3, as revealed by LEEP. Compared with patients with an initial normal cervical biopsy result, those with CIN 1 on initial biopsy were more likely to have CIN 3 on their LEEP findings (p =.08). Twenty-seven of 59 patients underwent a LEEP cone surgery; 1 of 27 had CIN 3 finding in the second-pass portion. This was associated with a CIN 3 identified on the first pass and associated with positive margins. The second pass of the LEEP cone failed to demonstrate CIN 96% of the time (p < .0001). Patients with a normal or a CIN 1 finding on the first pass had a normal finding on the second pass in 100% of cases. Conclusions. A LEEP cone is rarely indicated for the evaluation of a 2-step discrepancy. A randomized trial of this finding is warranted.

Rara vez está indicada una conización de cérvix mediante LEEP para resolver discrepancias de dos niveles

Objetivo. Entre las indicaciones actuales para practicar conización de cérvix está la resolución de crepancias dos niveles entre los resultados citológicos e tológicos. tamos de determinar la utilidad de la conización iante asa con electrocauterio (LEEP) para resolver discrepancias dos niveles. Métodos. Se llevó a cabo una revisión rospectiva obada por el comité de ética de las historias iacute;nicas de as las mujeres a las que se había recomendado una LEEP s detectar discrepancias entre un resultado citológico de ión escamosa intraepitelial de alto grado que había ivado el envío de la paciente y un resultado histológico mal o de neoplasia cervical intraepitelial (CIN) 1 en una psia colposcópica posterior; los casos diagnosticados de 2 se excluyeron del estudio. Los análisis estadísticos se realizaron con el software SAS 9 (SAS Institute, Inc., Cary, NC). Los resultados se consideraron significativos con un valor de p igual o inferior a 0,05. Resultados. A 59 pacientes se les había practicado una LEEP para resolver discrepancias de dos niveles entre los resultados citológicos e histológicos. A 27 pacientes se les practicó una segunda exéresis con asa del endocervix o conización mediante LEEP. De las pacientes con un resultado normal en la biopsia de cérvix y un resultado citológico de alto grado,10 (29%) de 34 presentaban resultados histológicos normales, en la LEEP, y 14 (41%) de 34 presentaban CIN 3; 16 (64%) de 25 pacientes con un resultado citológico de alto grado y un resultado de CIN 1 en la biopsia presentaban CIN 3, según lo indicado en la LEEP. En comparación con las pacientes con un resultado normal en la biopsia inicial de cérvix, aquellas con un resultado de CIN 1 en la biopsia inicial tenían más probabilidades de tener un resultado de CIN 3 en la LEEP (p = 0,08). A 27 de 59 pacientes se les había practicado una conización mediante LEEP; una de 27 presentaba un resultado de CIN 3 en el segundo paso, endocervical, del asa. Este caso se asoció con una CIN 3 identificada en el primer paso, ectocervical, del asa con márgenes positivos. El segundo paso del asa endocervical en la conización mediante LEEP no permitió demostrar la presencia de CIN en el 96% de los casos (p < 0,0001). Las pacientes con un resultado normal o de CIN 1 en el primer paso del asa obtuvieron un resultado normal en el segundo paso en el 100% de los casos. Conclusiones. Rara vez está indicada una conización mediante LEEP para la evaluación de una discrepancia de dos niveles. En este sentido, está justificada la realización de un estudio aleatorizado para analizar esta cuestión. ▪