Differential loss of heterozygosity profile on chromosome 3p in ductal and lobular breast carcinomas.

The 2 main histologic types of infiltrating breast cancer, invasive lobular and invasive ductal carcinoma, are morphologically and clinically distinct. Studies revealed that different patterns of gene expression and loss of heterozygosity can also distinguish these 2 subtypes. A whole-genome study using single nucleotide polymorphism array found a significantly higher frequency of loss of heterozygosity on 3p in invasive ductal carcinoma when compared with invasive lobular carcinoma. In this study, we performed a loss of heterozygosity analysis of the 3p chromosome region in ductal and lobular breast tumors. Seven microsatellite markers were evaluated in a series of 136 sporadic breast cancer cases (118 invasive ductal carcinoma and 18 invasive lobular carcinoma) and correlated with clinical-histopathologic parameters from the patients. A significantly higher frequency of loss of heterozygosity was observed in invasive ductal carcinoma (65.3%) when compared with invasive lobular carcinoma (38.9%). When the markers were analyzed separately, loss of heterozygosity at 3 of them, D3S1307 in 3p26.3, D3S1286 in 3p24.3, and D3S1300 in 3p14.2, were significantly more frequent in ductal than in lobular tumors. D3S1307 marker showed the highest frequency of loss of heterozygosity in invasive ductal carcinoma (46.2%), and associations between loss of this marker and loss of estrogen and progesterone receptors were found in these samples. Our results confirm the observations that invasive ductal carcinoma has a higher frequency of loss of heterozygosity events across the 3p region than invasive lobular carcinoma and show that specific losses on 3p26.3, 3p24.3, and 3p14.2 regions are more frequent in ductal than in lobular tumors. We discuss our data in relation to the known tumor suppressor genes that are mapped at the 3p loci investigated and their present relevant roles in breast cancer.

Lack of association between LOH in the 9p region and clinicopathologic parameters in primary breast cancer.

Previous studies have suggested the involvement of the 9p region in the genesis and progression of several types of cancer. To perform a more in-depth investigation of the 9p region in samples from breast carcinomas, we analyzed loss of heterozygosity (LOH) in 230 patients with primary breast cancer using five microsatellite markers spanning a genomic region of approximately 16.2 megabases. Genomic DNA was obtained from frozen tumor tissue, and peripheral blood was used as a normal reference. Among all samples, 171 (74%) were informative for at least 1 marker and 44 (25.73%) showed LOH. The LOH rates detected for all markers ranged from 10.29% (D9S169) to 15.97% (D9S1749). Among the informative cases for intragenic markers D9S1748 (CDKN2A) and D9S1749 (MTAP), we noticed a concordant loss of 90% (9/10). Associations between LOH frequencies and clinicopathologic parameters were found between marker D9S200 and tumor grade (P < 0.05), and between marker D9S1748 and estrogen receptor (ER) status (P < 0.05). In conclusion, our results agree with other data from the literature that point to LOH as a secondary mechanism of tumor suppressor inactivation on 9p in breast cancer, showing lower frequencies than those observed in other types of cancer. On the other hand, our results point to an interesting association between the concordant loss of genes CDKN2A and MTAP, which was not sufficiently explored in primary breast cancer.

Epidemiologia do câncer de mama em pacientes do Sul do Brasil / Epidemiology of breast cancer in patients from South of Brazil

O câncer de mama é a segunda neoplasia mais frequente em mulheres brasileiras. Dados do Instituto Nacional do Câncer (Inca) estimaram a ocorrência de 49.400 novos casos para o ano de 2008, no Brasil, com taxa de incidência de 51 casos a cada 100.000 mulheres. O Sul do País apresenta uma das mais altas taxas de incidência, com uma estimativa de 56,16 novos casos a cada 100.000 mulheres. Neste estudo, avaliamos 142 pacientes portadoras de carcinoma mamário, provenientes dessa região, em relação às características epidemiológicas e a parâmetros clínicos e histopatológicos. A média de idade das pacientes com diagnóstico confirmado foi de 57,7 + 13,7 anos; 17,6% apresentaram menarca precoce (antes dos 12 anos de idade); 14,7% apresentaram menopausa tardia (após os 55 anos); 18,1% eram nulíparas e 13,9% tiveram a primeira gestação após os 30 anos. Aproximadamente 40% das pacientes declararam ter feito uso de contraceptivos orais durante mais de dez anos e 24% eram fumantes. Grau tumoral II ou III foi observado em 81,1% das pacientes, presença de metástase em linfonodos regionais em 48% e tumor maior que 2 cm em 86%, indicando que o diagnóstico foi realizado em um estádio já avançado da doença. Considerando-se que a detecção precoce do câncer de mama é fator decisivo na determinação do prognóstico, estudos epidemiológicos em diferentes regiões do Brasil são importantes para o desenvolvimento de melhores programas de prevenção e rastreamento.