Biology of desmoplastic melanoma: a case-control comparison with other melanomas.

PURPOSE: Previous studies have established that patients with desmoplastic melanoma (DM) have thicker primary tumors. Consequently, comparisons with other forms of melanoma have been strongly biased by differences in Breslow stage. This is the first case-matched control study comparing DM with other forms of melanoma. PATIENTS AND METHODS: From a database of 3,202 melanoma patients treated at one institution, 89 patients with DM and 178 case-matched control patients (2:1) were identified by matching for tumor thickness, age, sex, and year of diagnosis. Clinical, pathologic, and outcome information was obtained from chart review. RESULTS: Controls were matched successfully to patients for tumor thickness, age, sex, and year of diagnosis. Presentation with American Joint Committee on Cancer stage III or IV disease is less common in patients with DM compared to case-matched control patients (5% v 21%; P < .001). Re-excisions to obtain clear surgical margins are required more often in patients with DM compared to case-matched control patients (21% v 6%; P < .001). Risk of positive sentinel nodes is lower in patients with DM compared to case-matched control patients (8% v 34%; P = .013). Despite these differences, survival rates of patients with DM are the same as case-matched control patients. CONCLUSION: Use of case-matched control patients matched for tumor thickness avoids biases introduced by the advanced Breslow stage of DMs. DMs are more locally aggressive than thickness-matched controls, and positive sentinel nodes are limited to patients with thick primary tumors. Importantly, patients with DM have survival rates similar to patients with other melanomas of similar thickness.

Reproductive cycle regulation of nuclear import, euchromatic localization, and association with components of Pol II mediator of a mammalian double-bromodomain protein.

Fsrg1 (female sterile homeotic-related gene 1) is the mouse homolog of the human RING3 protein, which has been shown to associate with the E2 promoter binding factor (E2F) transcription factor and to have a possible role in cell cycle-linked transcriptional regulation. The Fsrg1 protein is 60% identical in sequence to the RNA polymerase II mediator subunit Fsrg4, another member of this subfamily of double bromodomain-containing proteins that are homologs of Drosophila female sterile homeotic. Antibodies against murine Fsrg1 were generated and used in immunoblot and immunoprecipitation experiments to identify proteins interacting with Fsrg1 and RING3. In the presence of acetylated but not nonacetylated histone H3 and H4 peptides, RING3 was shown to interact with E2F, mediator components cyclin-dependent kinase 8 and thyroid receptor-associated protein 220, and the RNA polymerase II large subunit. Fsrg1 mRNA had been previously shown to be expressed at high levels in the epithelium of the adult mouse mammary gland. To determine the physiological relevance of these potential associations, we examined the patterns of expression of Fsrg1 mRNA and protein in the adult mammary epithelia during the reproductive cycle as the tissue is responding to estrogen, progesterone, and prolactin. Changes in the nuclear vs. cytoplasmic localization of Fsrg1 were observed and correlated with physiological changes in mammary gland function. The observations suggested that Fsrg1 may be involved in the transcriptional activities of genes involved in proliferation of the mammary epithelia during pregnancy and in orchestrating postlactation involution and apoptosis. Localization of Fsrg1 on euchromatin, the transcribed portion of the chromosomes, is consistent with its hypothesized function as a transcription regulator.

Melanoma in the young: differences and similarities with adult melanoma: a case-matched controlled analysis.

BACKGROUND: Melanoma in the first 2 decades of life is rare and is less well characterized than melanoma in adults. Previously published comparisons of melanoma of the young (age 13 years. CONCLUSIONS: Melanoma of the young had some important differences and similarities relative to adult melanoma. Lymph node metastases were more prevalent in young patients with melanoma compared with adult (thickness-matched) control patients; however, the 5- and 10-year survival rates were similar.

Mammographic screening: patterns of use and estimated impact on breast carcinoma survival.

BACKGROUND: Although many studies support the life-saving potential of screening mammography, the actual utilization of screening and the impact of the actual pattern of screening use on the breast carcinoma death rate, remain incompletely understood. In the current report, the authors describe patterns of screening use among women who were examined at a large screening and diagnostic service and estimate the added mortality associated with missed screening mammograms. METHODS: Mammography use was assessed in a population of 72,417 women who received a total of 254,818 screening mammograms at the Massachusetts General Hospital (MGH) Avon Comprehensive Breast Center (Boston, MA) between January 1, 1985, and February 19, 2002. A computer simulation of breast carcinoma growth, spread, and detection of breast carcinoma was used to estimate the likely health consequences of various types of screening use. RESULTS: Both prompt return for annual screening and full use of screening over extended periods of time were rare, and comparison of the MGH population with other populations revealed that the low level of use observed in the MGH population was not atypical. Only 6% of women who received a mammogram in 1992 received all annual mammograms that were available over the next 10 years; the mean number of mammograms received during this period was 5.06, or 51% of the number recommended by the American Cancer Society. Computer simulation results indicate that this underutilization of screening should result in higher mortality levels. Women from traditionally underserved socioeconomic, racial, and ethnic groups, women without insurance, and women who did not speak English had lower levels of use compared with other women. Lower levels of use also were observed among women receiving their first mammogram or who in the past had not returned promptly. Women ages 55-65 years had higher levels of use than did younger or older women. Women who previously had breast carcinoma also had higher levels of screening use. Nonetheless, none of the subpopulations of women stratified by age, race, ethnicity, zip code, income,language, insurance, status, previous screening use, or medical history exhibited a widespread propensity to promptly return for annual screening over an extended period of time. CONCLUSIONS: By many measures, the current analysis is one of the most detailed descriptions of screening use to date. The authors observed a level of screening use that was disappointingly low, with potentially negative health-related consequences, among women across categories defined by racial, ethnic, socioeconomic, and geographic characteristics; insurance status; language; age; medical history; and previous screening use. Improvements in the promptness with which women return to screening appear to have the potential to lead to considerable reductions in breast carcinoma death.

The age at which women begin mammographic screening.

BACKGROUND: The American Cancer Society recommends yearly mammographic screening for women starting at the age of 40 years. The authors examined the age at which women began screening at a large tertiary care center. METHODS: Utilization of mammography was assessed in a population of 72,417 women who received 254,818 screening mammograms at the Massachusetts General Hospital Avon Comprehensive Breast Center from January 1, 1985 to February 19, 2002, of which 940 received their first mammogram between January 16, 2000 and February 19, 2002. RESULTS: The median age at first mammogram for women in the population as a whole was 40.4 years. Sixty percent of women had their first mammogram by the end of their 40th year, and almost 90% had begun screening by age 50 years. However, these reassuring findings were not seen in several specific subpopulations of women. Black women began screening at a median age of 41.0 years, 0.7 years later than white women. Hispanic women began screening at a median age of 41.4 years, 1.1 years later than non-Hispanic women. Obese women began screening at a median age of 41.2 years, 1.6 years later than thin women. Women without a primary care physician began screening at a median age of 42.1 years, 1.8 years later than women with a primary care physician. Women without private health insurance began screening at a median age of 46.6 years, 6.3 years later than women with private health coverage. Women who did not speak English began screening at a median age of 49.3 years, 9.0 years later than women for whom English was the primary language. Women who both lacked private health insurance and spoke a language other than English began screening at a median age of 55.3 years, 15.2 years later than women without these characteristics. CONCLUSIONS: The analysis presented in the current study provided one of the most detailed descriptions of the age at screening initiation to be performed to date. Most women in the study population began screening by the end of their 40th year. This contrasted with the widespread failure of women to return promptly for subsequent annual examinations. However, specific subpopulations of women were at risk for not beginning screening on time, including women without private insurance, women without a primary care physician, and women who did not speak English. These findings suggest that there is little to be gained from populationwide efforts to encourage entry into the screening process, and that public health efforts should be focused on those subpopulations of women at highest risk for not using screening. These results also indicate that public health efforts to encourage women to start screening may be less critical than interventions to improve prompt return once they have entered the screening system.