Establishment of Histological Criteria for High-risk Node-negative Breast Carcinoma for a Multi-institutional Randomized Clinical Trial of Adjuvant Therapy

Tsuda, Hitoshi; Akiyama, Futoshi; Kurosumi, Masafumi; Sakamoto, Goi; Watanabe, Tôru

doi:10.1093/jjco/28.8.486

Cited by 97 publications

(87 citation statements)

References 19 publications

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“…The histological type of each tumor was evaluated based on a representative hematoxylin-eosin (HE) specimen of the tumor and a nuclear grade was assigned according to the standard scoring system (17)(18)(19).…”

Section: Methodsmentioning

confidence: 99%

FOXP3 expression of micrometastasis-positive sentinel nodes in breast cancer patients

Matsuura

Yamaguchi²,

Osaki³

et al. 2009

Oncol Rep

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Abstract. A number of methods have been established for identifying sentinel nodes (SNs). In the present study, we attempted to clarify the immunological status of SNs with or without micrometastasis in breast cancer patients. SNs were identified by the dye-and Á probe-guided method. Total RNA was extracted from the SNs, and the expression of T-BET, GATA-3, and FOXP3 were evaluated using quantitative realtime reverse transcriptase-polymerase chain reaction (RT-PCR). Micrometastasis was identified as microscopically negative but positive by RT-PCR specific for mammaglobin. Of 88 patients, 17 (19.3%) showed positive metastasis in SNs (pN1, 14; pN2, 3). Of the 71 metastasis-negative SNs, 11 showed positive bands on RT-PCR specific for mammaglobin [pN0(mol+)]. There was no significant correlation among clinicopathological features with or without micrometastasis. Immunological parameters were compared among the 60 pN0, 11 pN0(mol+), and 17 pN1-2. Although T-BET expression was higher in pN0(mol+) than pN0, FOXP3 expression was also higher in pN0(mol+) than pN0. In pN1-2, T-BET expression decreased compared with pN0(mol+), but FOXP3 expression did not. On the other hand, GATA-3 expression inversely increased in pN1-2 compared with pN0(mol+). In patients with breast cancer, micrometastasis can stimulate Th1 response in SNs. However, the Treg cell response is also induced at the micrometastasis level and persists during the progression of metastasis in SNs. Then, the shift in the Th1/Th2 balance may preferentially lean toward Th2 responses in pN1-2 SNs and suppress antitumor immune responses. Micrometastasis [pN0(mol+)] is a status immunologically distinguishable from pN0 and pN1-2.

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Section: Methodsmentioning

confidence: 99%

FOXP3 expression of micrometastasis-positive sentinel nodes in breast cancer patients

Matsuura

Yamaguchi²,

Osaki³

et al. 2009

Oncol Rep

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“…Using hematoxylin eosin-stained slides, the nuclear grade of all breast cancers was re-evaluated based on the histological criteria for breast carcinoma of the Japanese National Surgical Adjuvant Study of Breast Cancer (NSAS-BC), Pathology Section. 19,20) DNA methylation analysis of the BRCA1 gene From 32 frozen cancerous and non-cancerous tissues, each DNA was purified using the conventional phenol-chloroform method after homogenization and proteinase K digestion. The amount of DNA was quantified by absorbance measurements at 260 nm (UV).…”

Section: Methodsmentioning

confidence: 99%

BRCA1 Expression Status in Relation to DNA Methylation of the BRCA1 Promoter Region in Sporadic Breast Cancers

Niwa

Oyama

Nakajima

2000

Japanese Journal of Cancer Research

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To understand the biological role of BRCA1 in sporadic breast cancers, the relationship between DNA methylation of the BRCA1 promoter region and BRCA1 expression was studied using molecular biological and immunohistochemical methods. Furthermore, BRCA1 expression was compared with the expression of various cell cycle regulatory proteins and the morphological nuclear grade of cancer cells. Of 32 sporadic breast cancers investigated in this study, 10 (31%) revealed DNA methylation of the BRCA1 promoter region. The expression of BRCA1 was observed in the nuclei of cancer cells and 18 (56%) of 32 cancers were positive for BRCA1 immunoreactivity. Breast cancers with BRCA1 methylation lacked BRCA1 expression, except for only three cancers, and there was a significant inverse relationship between BRCA1 methylation and its expression in sporadic breast cancers (P = = = =0.043). Compared with the expression of various cell cycle regulatory proteins, breast cancers with BRCA1 methylation showed decreased expression of estrogen receptor (P = = = =0.016) and p27 (P = = = =0.018) and increased expression of p21 (P = = = =0.011). Furthermore, breast cancers without BRCA1 expression or with BRCA1 methylation had a tendency to contain nuclei with higher grade. These findings indicate that BRCA1 methylation might greatly influence its expression and BRCA1 expression might play an important role in cell cycle regulation and influence the grade of malignancy of sporadic breast cancers.Key words: BRCA1 -Expression -Immunohistochemistry -DNA methylation -Sporadic breast cancers BRCA1 has been identified by positioning cloning methods as a strong candidate for the 17q-linked gene for familial breast cancers and has been linked to more than 45% of familial breast cancers and 80% of families with breast and ovarian cancer.1) BRCA1 is a putative tumor suppressor gene located on chromosome 17q21 and spans 100 kb of genomic DNA, which encodes a protein of 220 kD consisting of 1863 amino acids.1) The BRCA1 protein is mainly localized in cell nuclei and is phosphorylated in a cell cycle-dependent manner.2) As regards subcellular nuclear localization, the BRCA1 protein has been reported to colocalize with Rad51, a homologue of bacterial RecA, in S phase cells, 3) which suggests a role for BRCA1 in the control of recombination and of genome integrity. However, the exact biological function of BRCA1 still remains unclear.More than 300 germline mutations have been identified so far in patients with familial breast and/or ovarian cancer.1, 4) These mutations are distributed across the entire coding region of the BRCA1 gene, and the majority is predicted to result in truncated proteins or loss of a BRCA1 transcript. Therefore, mutations in the BRCA1 gene may play a significant role in the tumorigenesis of familial breast cancer. 5,6) Though it has been shown that BRCA1 mRNA levels are reduced or absent in both sporadic and familial breast cancer, 7, 8) a few somatic mutations in the BRCA1 gene have been identified in sporadic breast cancers.9) Fr...

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“…Lymph node status was determined by counting the number of axillary lymph nodes with histological evidence of metastatic breast carcinoma. Histological typing and nuclear grading were performed as described elsewhere (25,26), respectively.…”

Section: Covariatesmentioning

confidence: 99%

Clinicopathological Significance of Vascular Endothelial Growth Factor-C in Breast Carcinoma with Long-Term Follow-Up

et al. 2003

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Establishment of Histological Criteria for High-risk Node-negative Breast Carcinoma for a Multi-institutional Randomized Clinical Trial of Adjuvant Therapy

Cited by 97 publications

References 19 publications

FOXP3 expression of micrometastasis-positive sentinel nodes in breast cancer patients

FOXP3 expression of micrometastasis-positive sentinel nodes in breast cancer patients

BRCA1 Expression Status in Relation to DNA Methylation of the BRCA1 Promoter Region in Sporadic Breast Cancers

Clinicopathological Significance of Vascular Endothelial Growth Factor-C in Breast Carcinoma with Long-Term Follow-Up

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