Faculty Bibliography

OBJECTIVE:We undertook an extensive molecular characterization of the epidermal growth factor receptor (EGFR) gene in vulvar squamous cell carcinomas to investigate EGFR mutation and/or genomic amplification and its association with EGFR protein expression, high-risk human papillomavirus (HPV) status and clinical outcome. METHODS:A cohort of 51 vulvar cancer patients distributed across all FIGO stages was selected for immunohistochemistry (IHC) and fluorescence in situ hybridization. EGFR expression and gene amplification were correlated with high-risk HPV status, EGFR mutational status and clinical prognostic variables. Fisher's exact tests, Kaplan-Meier survival estimates and a Cox proportional-hazards model were utilized. RESULTS:EGFR gene amplification and chromosome 7 high polysomy were observed in 12% and 6% of cases, respectively. IHC of malignant tissue with 3+ staining demonstrated 100% sensitivity and 79% specificity to detect EGFR gene amplification, yielding a 39% positive predictive value. Decreased survival (p<0.025) was observed in patients with gene amplification, and was associated with a more statistically robust 3.3 hazard ratio (p<0.005) in the Cox proportional-hazards model that controlled for age at diagnosis, stage and lymph node metastasis. Univariate analysis confirmed that EGFR gene amplification was associated with the absence of high-risk HPV (p<0.001). Common activating EGFR gene mutations were not identified. CONCLUSION/CONCLUSIONS:A subset of patients with vulvar squamous cell carcinoma was identified with EGFR gene amplification that was HPV-independent and associated with poor prognosis. Given the association of EGFR amplification with response to targeted therapy in other tumor types, these patients may be candidates for therapeutic strategies that target the EGFR pathway.

OBJECTIVE:To describe a novel Müllerian anomaly and management options. DESIGN/METHODS:Case series report. SETTING/METHODS:Metropolitan tertiary care children's hospital. PATIENT(S)/METHODS:Three caucasian girls, aged 12, 13, and 15 years, with a novel congenital anomaly. INTERVENTION(S)/METHODS:Interval staged vaginoplasties. MAIN OUTCOME MEASURE(S)/METHODS:Functional vagina. RESULT(S)/RESULTS:Didelphys Müllerian development with vaginal duplication and agenesis of both lower vaginas with staged vaginoplasties resulting in normal functional vaginas. CONCLUSION(S)/CONCLUSIONS:Staged pull-through vaginoplasties led to functional outcome in this unusual anomaly.

The recent recognition of oncogenic human papillomavirus (HPV) as a key component of female lower genital tract malignancies has led to significant changes in many screening and prevention guidelines for cervical cancer, and, combined with the advent of vaccination, will likely have sweeping repercussions on the incidence of cervical, vulvar, and vaginal carcinoma. This article focuses on the specific principles of cancer screening and prevention with an emphasis on HPV-mediated disease.

OBJECTIVE:To develop human chorionic gonadotropin (hCG) criteria that determine a patient's risk of developing persistent gestational trophoblastic neoplasia (GTN) or achieving remission after partial mole evacuation. STUDY DESIGN/METHODS:We used a database from the New England Trophoblastic Disease Center to analyze hCG levels from 284 women with partial molar pregnancies diagnosed between 1973 and 2003. RESULTS:An hCG level >199 mIU/mL in the third through eighth week following molar evacuation was associated with at least a 35% risk of GTN. CONCLUSION/CONCLUSIONS:Women with partial mole who have elevated hCG levels within the first few weeks after molar evacuation are at increased risk for developing GTN.

OBJECTIVE:We evaluated the risk of gestational trophoblastic neoplasia (GTN) for women with partial molar pregnancy whose human chorionic gonadotropin (hCG) levels fall spontaneously to undetectable levels using a sensitive hCG assay. METHODS:We analyzed data from the New England Trophoblastic Disease Center to estimate the risk of GTN among 284 women with partial molar pregnancy and at least 6 months of gonadotropin follow-up. RESULTS:None of the 238 women with complete gonadotropin follow-up and a spontaneous decline in serum hCG levels to undetectable levels subsequently developed GTN (95% confidence interval 0-1.6%). CONCLUSION/CONCLUSIONS:If these results are replicated at other institutions with longstanding experience managing partial molar pregnancies, it may be reasonable to abbreviate clinical follow-up for women with partial molar pregnancy whose serum hCG levels spontaneously decline to an undetectable level.

OBJECTIVE:To identify clinical characteristics associated with developing persistent gestational trophoblastic neoplasia (GTN) after partial hydatidiform molar pregnancy (PHM). STUDY DESIGN/METHODS:Utilizing the Donald P. Goldstein in patients who developed persistence between 1973 and 1989. CONCLUSION/CONCLUSIONS:Older age at diagnosis and history of prior mole were significantly more common in women who developed persistence after partial molar pregnancy in referral of patients the earlier cohort but not in idefined clinical the recent cohort. In recent years no clinical factor was at increase their risk significantly associated with rsistence. database at the New England Trophoblastic Disease Center, 284 women with partial molar pregnancy diagnosed between 1973 and 2003 were characteristics identified. Clinical charac- for pe teristics, such as gravidity, parity, age, uterine size, gestational age at diagnosis, human chorionic gonadotropin levels at presentation and time to development of persistence (GTN) were analyzed. Data were also divided into 2 cohorts, an earlier one (1973-1989) and a later one (1990-2003), in order to look at potential changes over time. RESULTS:GTN developed in 5.6% of partial molar pregnancies. Older maternal age was significantly associated with development of persistent GTN in the earlier cohort but not in the recent cohort. Previous molar pregnancy was also statistically significantly more common the development of +/-after PHM.