We have previously demonstrated that the transition of melanoma to the metastatic phenotype is associated with a loss of expression of the transcription factor AP-2. To further investigate the role of AP-2 in the progression of human melanoma, we attempted to inactivate AP-2 in primary cutaneous SB-2 melanoma cells by using a dominant-negative AP-2, or AP-2B, gene. AP-2B is an alternatively spliced AP-2 variant capable of inhibiting AP-2 trans-activator function. Stable transfection of primary cutaneous melanoma SB-2 cells with the dominant-negative AP-2B gene was con®rmed by RT ± PCR and Northern blot analyses. Electromobility shift assay using nuclear extracts from these cell lines demonstrated decreased functional binding of AP-2B-transfected cells to the AP-2 consensus binding sequence compared with neo-transfected controls. In addition, CAT activity driven by a construct containing the AP-2 consensus binding sequence was downregulated in the AP-2B transfected cells, indicating AP-2 activity was quenched in the transfected cells. Orthotopic (subcutaneous) injection of the dominant-negative (AP-2B)-transfected cell lines into nude mice increased their tumorigenicity compared to control neo-transfected cells. The AP-2B-transfected cells displayed an increase in MMP-2 expression (by Northern blot) and MMP-2 activity (by zymography), which resulted in an increase in invasiveness through Matrigel-coated ®lters. The AP-2B-transfected tumors also displayed an increase in MMP-2 expression, microvessel density, and angiogenesis in vivo. These results demonstrate that inactivation of AP-2 contributes to the progression of melanoma, at least partially via deregulation of the MMP-2 gene.

BACKGROUNDSentinel lymphadenectomy reliably identifies the first site(s) of regional lymphatic drainage and, therefore, the most likely lymph nodes to contain occult metastasis in patients with primary cutaneous melanoma. Although in most patients lymphatic drainage from the primary melanoma first reaches a standard lymph node basin, a sentinel lymph node (SLN) may be identified in an unusual location. The objective of this study was to determine the frequency and significance of unusual sentinel lymph node drainage patterns in a large cohort of patients with primary melanoma.METHODSThe records of 1145 consecutive primary melanoma patients who underwent SLN biopsy were reviewed. Preoperative lymphoscintigraphy was performed in all patients with truncal melanoma and in many patients with distal extremity lesions. Unusual lymph node sites were defined as epitrochlear, popliteal, or ectopic/interval (in‐transit or any other nonstandard lymph node‐bearing area).RESULTSAt least one SLN was harvested in 1117 patients (98%). SLN biopsy of an unusual lymph node site was attempted in 59 patients (5%). Successful intraoperative localization and biopsy was performed in 54 (92%) of 59 patients for a total of 56 unusual sites. Of these, 7 (13%) were popliteal, 8 (14%) were epitrochlear, and 41 (73%) were ectopic/interval. Preoperative lymphoscintigraphy was performed in 41 of these 54 patients and correctly identified unusual SLN locations in 12 (29%); the majority of unusual SLNs were identified only with the assistance of the intraoperative gamma probe. In four patients (7%), the unusual lymph node site was the only site from which SLNs were harvested. In the remaining 50 patients (93%), biopsies were performed on SLNs from both unusual sites and from a standard lymph node basin. Among the 54 patients who underwent a SLN biopsy of an unusual nodal site, 7 (13%) had lymph node metastases in that location. In four of the seven patients, the only positive SLN was from the unusual site.CONCLUSIONSSentinel lymphatic drainage patterns include lymph node‐bearing areas that may be outside established standard lymph node basins and may represent the only site of regional lymph node metastases. Although preoperative lymphoscintigraphy may assist in the identification of unusual SLN drainage patterns, intraoperative use of the gamma probe is recommended to identify accurately and completely all sites of regional lymph node drainage. Cancer 2002;95:354–60. © 2002 American Cancer Society.DOI 10.1002/cncr.10664

The incidence of pulmonary and gastrointestinal carcinoids has dramatically increased since 1981. Tumor location and age > or = 60 years are the strongest predictors of mortality.

The incidence of DCIS has risen dramatically with the advent of screening mammography. Increasing numbers of these patients are treated with BCT, although a large proportion are still treated with mastectomy, in some cases combined with axillary dissection. Sentinel lymph node biopsy and tamoxifen are important components of therapy, the use of which is slowly increasing in the treatment of DCIS.

In this first-ever systematic review of fetal alcohol spectrum disorders in all federal court cases arising prior to 2011, the authors identified 1713 cases, with 131 cases substantively relevant to mental capacity, criminal intent, sentencing, and attorney malpractice. The majority of cases arose after Atkins v. Virginia, the pivotal Supreme Court case that prohibits the death penalty for mentally disabled persons. Among other things, this study reveals that FASD evidence usually defeats a death penalty sentence, but the lower courts reflect inconsistencies in how courts receive and handle mental health evidence.