Estrogen levels increase during pregnancy and clinical evidence has long suggested that melanocytes are estrogen-responsive. We hypothesized that nevi from pregnant patients would exhibit increased expression of estrogen receptor β (ERβ) and thus enhanced potential to respond to altered estrogen levels. Normal, dysplastic and congenital nevi (n = 212) were collected from pregnant and nonpregnant women ranging from 18 to 45 years of age. Immunohistochemical staining was performed on these nevi using antibodies specifically directed against estrogen receptor α (ERα) and ERβ. ERα was not observed in any lesions; thus, ERβ was the predominant estrogen receptor in melanocytic cells from all types of nevi. Enhanced positivity for ERβ in normal nevi during pregnancy was noted, compared with non-pregnant controls including nevocytes residing in both the epidermal and dermal micro-environments (P = 0.005 and P = 0.001 respectively). Nevi with increasingly melanocytic atypia showed increased ERβ in nevocytes nested within the epidermis. No additional increase in ERβ in atypical nevi was observed during pregnancy. For normal and congenital nevi, regardless of pregnancy status, dermally associated nevocytes tended to have greater ERβ immunoreactivity. Significant decreases in ERβ immunoreactivity were observed in congenital nevi from pregnant women compared with normal and dysplastic nevi from pregnant women. Our data suggest that nevi possess the capacity to be estrogen-responsive. Factors such as pregnancy and degree of atypia are associated with enhanced ERβ with the exception of congenital nevi where the melanocytes were unique in their response to pregnancy.
The Melanoma Staging and Classification system was recently revised by the American Joint Committee on Cancer (AJCC) and implemented effective January 2010 with changes reflecting new prognostic data gleaned by the significantly larger patient population studied for the 7th edition. This newest analysis yields important long-term outcome data as many of the patients were followed for nearly 2 decades. Additions to edition 7 of the AJCC Melanoma Staging classification highlight several important prognostic factors, particularly the addition of mitotic rate for classifying thin melanomas, the presence of microtumor burden in lymph nodes for stage III disease, and elevated lactate dehydrogenase levels in patients with distant metastatic disease. Although the basic tumor-nodes-metastases (ie, TNM) cancer classification model remains unchanged in this newest edition, the current AJCC Melanoma Staging System has incorporated the latest prognostic data to accurately stratify patients into staging categories. It is important for clinicians and dermatopathologists to familiarize themselves with these changes so that patients are suitably managed and referred to medical and surgical oncologists when appropriate.
Therapeutic target with β blockers in heart failure, i.e., target heart rate reduction or β‐blocker dose, is controversial. To resolve this controversy, the authors studied 152 heart failure patients on β blockers who were divided into four groups based on median peak exercise heart rate reduction as compared with predicted and prescription of at least 50% recommended β‐blocker dose. Event‐free survival (vs. death or assist device placement or urgent transplantation) was compared. Baseline and peak exercise heart rates were 74±14 and 116±21 bpm, respectively. Median heart rate reduction at peak exercise was 35%. When median or higher peak heart rate reduction was achieved, there were no significant survival differences noted between patients on different β‐blocker doses. With below‐median peak heart rate reduction, there was a strong trend toward better event‐free survival with higher β‐blocker doses. In conclusion, the results suggest that higher heart rate reduction is associated with better outcomes for heart failure patients overall and, for patients with persistently elevated heart rates, higher β‐blocker doses provided additional benefit.
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