Search

Abstract. As at present only a long-term follow-up can fully determine whether monoclonal gammapathies of undetermined significance (MGUS) will evolve into multiple myeloma (MM), this study attempted to identify other variables connected with the amount of monoclonal component (MC), generally considered as the most reliable marker of malignant evolution. Thirty-four MGUS subjects showing a high MC (≥ 15.0 g/l) but without clinical evidence of MM (MGUS group b), were characterized for their phenotypic and genotypic profile by comparing them either with 40 MM patients or with 24 subjects affected by a benign form of monoclonal gammapathy (MGUS group a) according to the standard criteria. In addition to the usual laboratory markers, the levels of expression of a panel of CD membrane subsets were measured on B and T lymphocytes. Also, the serum level of the p53 mutant protein and the structural alterations of the c-myc oncogene were evaluated. The results show that for MGUS group b patients, an increased M-protein was accompanied by significantly increased levels of peripheral blood CD3 + T cells and oncogenetic aberrations in c-myc . Since a high serum MC level seems to indicate a greater likelihood of malignant transformation for MGUS patients, these findings suggest that this relationship may be a result of the concomitant alterations observed at a phenotypic and genotypic level. Such alterations may be potentially useful as surrogate markers for the transition of benign to malignant (MM) plasma cell dyscrasia. [ABSTRACT FROM AUTHOR]

This report describe the case of a patient presenting with pulmonary metastases from a penile cancer, where the presence of the human papillomavirus (HPV) type 16 DNA both in the primary tumor and in the distant metastases confirmed the spreading of the disease, ruling out a possible primary lung squamous cell carcinoma. Indeed, according to the findings, the HPV genotyping test might help in the identification of metastatic disease from anogenital malignancies or other HPV-related cancers.

Introduction: The risk of colorectal cancer (CRC) after BC and the additional risk factor of tamoxifen exposure were investigated by several studies with conflicting results. We performed a case-control study aimed at investigating if a past history of breast cancer is a risk factor of developing adenomas or CRC and establishing whether tamoxifen exposure is an additional risk factor., Materials and Methods: We enrolled 175 asymptomatic women with a past history of BC and invited them to undergo a screening colonoscopy. In the same period, we enrolled 201 healthy asymptomatic women (HG) with no family history of CRC which were referred to our Unit for a colonoscopy., Results: Mean age at colonoscopy was 56.9 years for BC patients vs. 56.3 years for HG (p=0.58). In 32/175 (18.3%) BC patients, 38 lesions and in 17/201 (8.4%) controls, 20 lesions (p=0.029) were diagnosed. BC patients had 5/32 CRC vs. no CRC in the HG. Multivariate analysis of age, family history of CRC, timing from BC diagnosis and first colonoscopy, tamoxifen treatment revealed that none of the variables were predictive of the presence or absence of adenomas or CRC in the BC group., Discussion: In the present study BC group had a significant higher prevalence of adenoma or CRC than controls. Tamoxifen exposure did not increase the risk of adenoma or CRC. Our data support the hypothesis that BC is a risk condition for adenomas or CRC. The risk is small but present and a screening colonoscopy should be offered to these patients., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Introduction: Estrogen receptor-alpha (ER-alpha) and progesterone receptor (PgR) are consolidated predictors of response to hormonal therapy (HT). In contrast, little information regarding the role of estrogen receptor-beta (ER-beta) in various breast cancer risk groups treated with different therapeutic regimens is available. In particular, there are no data concerning ER-beta distribution within the novel molecular breast cancer subtypes luminal A (LA) and luminal B (LB), HER2 (HS), and triple-negative (TN)., Methods: We conducted an observational prospective study using immunohistochemistry to evaluate ER-beta expression in 936 breast carcinomas. Associations with conventional biopathological factors and with molecular subtypes were analyzed by multiple correspondence analysis (MCA), while univariate and multivariate Cox regression analysis and classification and regression tree analysis were applied to determine the impact of ER-beta on disease-free survival in the 728 patients with complete follow-up data., Results: ER-beta evenly distributes (55.5%) across the four molecular breast cancer subtypes, confirming the lack of correlation between ER-beta and classical prognosticators. However, the relationships among the biopathological factors, analyzed by MCA, showed that ER-beta positivity is located in the quadrant containing more aggressive phenotypes such as HER2 and TN or ER-alpha/PgR/Bcl2- tumors. Kaplan-Meier curves and Cox regression analysis identified ER-beta as a significant discriminating factor for disease-free survival both in the node-negative LA (P = 0.02) subgroup, where it is predictive of response to HT, and in the node-positive LB (P = 0.04) group, where, in association with PgR negativity, it conveys a higher risk of relapse., Conclusion: Our data indicated that, in contrast to node-negative patients, in node-positive breast cancer patients, ER-beta positivity appears to be a biomarker related to a more aggressive clinical course. In this context, further investigations are necessary to better assess the role of the different ER-beta isoforms.

We aimed at developing a more detailed understanding of cyclin D1 in early stage human breast cancer and defining the biologic profiles with different prognostic value correlating cyclin D1 gene amplification and chromosome 11 aneusomy with bio-pathologic variables of known clinical importance. Cyclin D1 gene amplification and chromosome 11 aneusomy were investigated using fluorescence in situ hybridization whereas cyclin D1, PgR, HER-2, Bcl2, p53, and Ki-67 expressions were analyzed by immunohistochemistry in 121 stage I or II breast cancer patients uniformly treated with cyclophosphamide/metotrexate/5-fluorouracil-based chemotherapy. Cyclin D1 was amplified in 6.6% and overexpressed in 32.2% of cases. Amplification was not associated with any selected bio-pathologic variables, whereas the chromosome 11 aneusomy level significantly increased in tumors with higher histologic grade (P < 0.01), higher tumor size (P < 0.003), p53 nuclear accumulation (P < 0.04), and ERalpha negativity (P < 0.049). Multiple correspondence analysis showed 4 different biologic tumor profiles. The first, characterized by high Ki-67 score, p53+, cyclin D1+, HER-2+, aneusomy level > 30%, ratio (cyclin D1 gene/CEP11) > 2, was associated with tumor relapse defining the most unfavorable biologic profile. Kaplan-Meier's method showed significantly shorter disease-free survival in patients with at least 3 variables positive out of the 6 detected by multiple correspondence analysis. In multivariate analysis, the identified biologic profile emerged as the only significant prognostic indicator. Our findings are of particular clinical interest for early stage breast cancer patients, because the assessment of biologic factors predictive of tumor aggressiveness may influence postoperative therapeutic strategies.