The clinical significance of massive intratumoral lymphocytosis in squamous cell carcinoma of the anus.

A recent report indicates that patients with squamous cell carcinoma of the anal canal (SCCAC) and intraepithelial lymphocytes have a poor prognosis. Against that background, histological sections from 277 consecutive SCCACs were reviewed searching for cases with massive tumor-infiltrating lymphocytes (TILs; >/= 50 lymphocytes /100 tumor cells). Of the 277 SCCACs, 8 (3%) had massive TILs. These 8 patients (all females) had both more advanced clinical stage than the remaining 269 control SCCAC patients. Follow-up studies revealed that the 8 patients with SCCACs having massive TILs had a much better 15 years survival rate than control SCCAC patients. It is concluded that despite SCCAC patients with massive TILs had a more advanced clinical stage than SCCAC controls, SCCAC with massive TILs patients had a longer survival rate (with no deaths after 5 years) than control cases. The search via proteomic methodology for the lymphocyte-attracting tumor protein might bring forward a novel co-adjuvant therapy, capable to increase prolonged survival time in patients having SCCAC without massive TILs.

Pronounced chromosomal instability and multiple gene amplifications characterize ulcerative colitis-associated colorectal carcinomas.

Patients with ulcerative colitis have a significantly increased lifetime risk for the development of colorectal carcinomas. While genetic and genomic changes during carcinogenesis have been thoroughly studied in sporadic colorectal cancers, less is known about ulcerative colitis-associated colorectal carcinomas. The aim of this study was to extend the identification of specific genomic imbalances to ulcerative colitis-associated colorectal carcinomas and to establish a comprehensive map of DNA gains and losses by investigating 23 tumor specimens from 23 patients. The molecular cytogenetic characterization was performed using comparative genomic hybridization; immunohistochemistry was used to measure proliferative activity and laminin-5 expression as a marker for invasiveness. The results indicate that these tumors are invariably aneuploid, with a high proliferative activity and increased invasive potential. The average number of copy alterations correlates with increased cyclin A levels (P=0.044), which is an independent predictor of risk of carcinoma development in ulcerative colitis. Despite severe genetic instability, the general pattern of specific chromosomal aberrations that defines sporadic colorectal carcinomas is maintained in ulcerative colitis-associated malignancies. High-level copy number increases (amplifications) are dispersed throughout the genome. Strikingly, these amplifications are much more frequent than in sporadic carcinomas and map to chromosomal regions that have not been described before.

DNA amplifications and aneuploidy, high proliferative activity and impaired cell cycle control characterize breast carcinomas with poor prognosis.

In order to explore whether specific cytogenetic abnormalities can be used to stratify tumors with a distinctly different clinical course, we performed comparative genomic hybridization (CGH) of tumors from patients who were diagnosed with metastatic disease after an interval of less than 2 years or who remained free from distant metastases for more than 10 years. All patients presented with distant metastases after mastectomy indicating that none of the patients in this study was cured and free of remaining tumor cells. Tumors in the group of short-term survivors showed a higher average number of chromosomal copy alterations compared to the long-term survivors. Of note, the number of sub-chromosomal high-level copy number increases (amplifications) was significantly increased in the group of short-term survivors. In both short- and long-term survivors recurrent chromosomal gains were mapped to chromosomes 1q, 4q, 8q, and 5p. Copy number changes that were more frequent in the group of short-term survivors included gains of chromosome 3q, 9p, 11p and 11q and loss of 17p. Our results indicate that low- and high grade malignant breast adenocarcinomas are characterized by a specific pattern of chromosomal copy number changes. Furthermore, immunohistochemical evaluation of the expression levels of Ki-67, p27KIP1, p21WAF1, p53, cyclin A and cyclin E revealed a correlation between increased proliferative activity and poor outcome.

Vascular growth factor expression in a rat model of severe limb ischemia.

BACKGROUND: In ischemic tissue hypoxia induces production of vascular growth factors, especially VEGF, which initiate local angiogenesis. Collateralization-or arteriogenesis-occurs at a distance from the ischemic tissue and depends on different growth factors such as FGF-2. A spatial discrepancy in endogenous growth factor production in limb ischemia may have implications for therapeutic angiogenesis. The present study elucidates if such spatial and temporal variation occurs. MATERIALS AND METHODS: A two-staged procedure was performed to generate severe long-lasting limb ischemia in 60 rats. At 1, 7, 28, and 56 days, subgroups were subjected to perfusion assessment with laser Doppler imaging and angiography. Muscle samples and foot skin were gathered to measure growth factor expression and signs of angiogenesis using immunohistochemistry. RESULTS: There was an early twofold increase (P < 0.05) in both VEGF and FGF-2 levels in distal muscle from the ischemic leg, but no significant rise in the thigh. The concentrations decreased over time with an exception for VEGF in soleus and FGF-2 in anterior tibial muscle, which remained high. An increased capillarity was noted (P < 0.05) in soleus after 28 days, and the number of BrdU-positive ECs was elevated in all ischemic samples at 56 days. Collateral arteries were observed on the angiograms after 7 days. CONCLUSIONS: The results suggest that in limb ischemia any major increase in vascular growth factor production is limited to ischemic tissue. The spatial and temporal distribution patterns of growth factor production are complex and to a great extent influenced by inflammation.