Cutaneous malignant melanoma remains the leading cause of skin cancer death in industrialized countries. Clinical and histological variables that predict survival, such as Breslow's index, tumor size, ulceration, or vascular invasion have been identified in malignant melanoma. Nevertheless, the potential relevance of biological variables still awaits an in-depth exploration. Using tissue microarrays (TMAs), we retrospectively analyzed 165 malignant melanoma samples from 88 patients corresponding to distinct histological progression phases, radial, vertical, and metastases. A panel of 39 different antibodies for cell cycle, apoptosis, melanoma antigens, transcription factors, DNA mismatch repair, and other proteins was used. Integrating the information, the study has identified expression profiles distinguishing specific melanoma progression stages. Most of the detected alterations were linked to the control of cell cycle G1/S transition; cyclin D1 was expressed in radial cases 48% (12 of 25) with significant lost of expression in vertical cases 14% (9 of 65), P = 0.002; whereas p16(INK4a) (89% in vertical versus 71% in metastatic cases, P = 0.009) and p27(KIP1) (76% in radial versus 45% in vertical cases, P = 0.010) were diminished in advanced stages. The study also defines a combination of biological markers associated with shorter overall survival in patients with vertical growth phase melanoma, that provided a predictor model with four antibodies (Ki67, p16(INK4a), p21(CIP1), and Bcl-6). This predictor model was validated using an independent series of 72 vertical growth phase melanoma patients.

Background. Occult carcinoma of the thyroid (OCT) seems to be present in a significant proportion of the general population. Previous studies have shown large variations in the prevalence rate of OCT, which may be due to differences in the prevalence rates between different geographic areas, but also to the lack of standardized diagnostic criteria and methods of examination. The epidemiologic features of OCT at autopsy in Spain are reported for the first time. Methods. To investigate the influence of methodology in the results, two series were studied, each one using a different method. In Series A, 625 cases were studied, and sections were taken only from grossly visible lesions. In Series B, the whole thyroid glands of 100 autopsies were cut into blocks and all blocks were histologically studied. In addition, immunocytochemical stainings were performed in Series B for calcitonin, thyroglobulin, and epidermal keratin. Results. Series A found 33 OCTs (5.28%), consisting of 29 occult papillary carcinomas (OPC), 2 occult follicular carcinomas, 1 occult oxyphilic carcinoma, and 1 occult medullary carcinoma. Series B found 22 OPC cases (22%) containing a total of 53 tumor foci. Tumor diameter varied from 0.07 to 1.8 mm. The epithelial cells of all the OPC were negative for calcitonin, weakly positive for thyroglobulin, and intensely positive for epidermal keratin. One case had metastasis in a regional lymph node. Conclusions. This study shows that the differences in the incidence of OCT found in numerous studies are due not only to actual different geographic incidences but also to the method of study.

Head and neck squamous cell carcinoma (HNSCC) is a common human neoplasia with poor prognosis and survival that frequently displays Akt overactivation. Here we show that mice displaying constitutive Akt activity (myrAkt) in combination with Trp53 loss in stratified epithelia develop oral cavity tumors that phenocopy human HNSCC. The myrAkt mice develop oral lesions, making it a possible model of human oral dysplasia. The malignant conversion of these lesions, which is hampered due to the induction of premature senescence, is achieved by the subsequent ablation of Trp53 gene in the same cells in vivo. Importantly, mouse oral tumors can be followed by in vivo imaging, show metastatic spreading to regional lymph nodes, and display activation of nuclear factor-KB and signal transducer and activator of transcription-3 pathways and decreased transforming growth factor-B type II receptor expression, thus resembling human counterparts. In addition, malignant conversion is associated with increased number of putative tumor stem cells. These data identify activation of Akt and p53 loss as a major mechanism of oral tumorigenesis in vivo and suggest that blocking these signaling pathways could have therapeutic implications for the management of HNSCC.

ABSTRACT— The authors report 24 cases of diffuse nodular regenerative hyperplasia of the liver (DNRH) seen in a General Hospital during the last 9 years (prevalence: 3'1/100 000, incidence: 0'34/100 000). DNRH was diagnosed in 0.52% of the liver biopsies and 0.72 of the autopsies. These results suggest that DNHR is probably more frequent than suspected, and 1 DNRH was seen for each 39 biopsied cases of liver cirrhosis. Fourteen patients did not have hepatic symptoms. Portal hypertension was present in 9 cases. The biochemical disturbance most frequently found was a moderate elevation of GGT and APh, associated with slight elevation of SGOT, SGPT and bilirubin levels. Normal liver function tests could be seen (3 cases). Previous exposure to potentially hepatotoxic drugs or chemicals was discovered in 15 cases (62.5%). Diseases associated were circulatory disturbances (6 cases), autoimmune disease (5 cases), hemopathies (5 cases), and visceral carcinomas (4 cases). Two patients were recipients of renal transplant. Nodules distributed through the whole liver tissue were found in 16 cases, while 8 patients showed areas of normal parenchyma in their livers. Impairment of small hepatic vessels was detected in 16 cases. Some uneven cytologic findings were discovered: clusters of small basophilic cells (4 cases), large clear cells (8 cases), and dysplastic hepatocytes (10 cases), which suggests that DNRH could be a preneoplastic condition.