GSTPi-positive tumour microenvironment-associated fibroblasts are significantly associated with GSTPi-negative cancer cells in paired cases of primary invasive breast cancer and axillary lymph node metastases.

BACKGROUND: Glutathione S-transferase Pi (GSTPi) expression is one of the factors, which is known to be associated with development of resistance to chemotherapeutics in cancer patients, including those with breast cancer. Yet, its expression has been reported to be undetectable in cancer cells in high percent of patients with primary breast cancer. However, GSTPi expression in stromal cells in breast tumour microenvironment, namely cancer-associated fibroblast (CAF), which is recognised to have major roles in cancer progression, remains poorly reported. METHODS: The aim of the study was to determine the expression of GSTPi; vimetin, a fibroblast-associated cytoskeleton protein; and α-smooth muscle actin (α-SMA), a known marker of CAF in breast cancer tissue, by immunohistochemical staining method in consecutive histologic sections of formalin-fixed and paraffin-embedded tissue biopsy specimens from a cohort of 39 paired cases of patients with invasive breast cancer and the corresponding axillary lymph nodes metastases. RESULTS: Ductal and acinar luminal epithelial cells, myoepithelial cells and surrounding fibroblasts exhibited a homogeneous cytoplasmic reactivity with anti-GSTPi antibody in 11 of 11 cases of benign breast tissue biopsies. The vimentin-positive fibroblasts were unreactive with anti-α-SMA antibody. Loss of GSTPi expression was observed in breast cancer cells, at both the primary and metastatic sites, in 31 of 39 paired cases, as compared with benign breast epithelial cells (Fisher's exact test P<0.001). A significant association was observed between GSTPi-positive, vimentin-positive and α-SMA-positive fibroblast in tumour microenvironment at both sites. CONCLUSION: This is an original report of demonstration of a significance association between tumour microenvironment-associated GSTPi-positive CAF (vimentin/α-SMA-positive) and the GSTPi-negative cancer cells in paired cases of primary invasive breast cancer and the corresponding axillary lymph nodes metastases.

Can radiographic plain film be used to determine the depth of the tumour bed in the absence of surgical clips for breast boost planning.

PURPOSE: A number of studies have demonstrated the importance of using surgical clips to define the tumour bed in breast boost radiotherapy. In the absence of such clips, other techniques suggested to improve boost location have included CT and ultrasound (US). Determination of the depth of the tumour bed is important in the selection of electron energy. This study was conducted to prospectively compare the depth of the lumpectomy cavity as defined by ultrasound to radiographic plain film evaluation of the anterior border of the pectoralis muscle. MATERIALS AND METHODS: Forty-one breast-cancer patients treated at the Division of Therapeutic Radiology and Oncology, Department of Radiology, Faculty of Medicine, Chiang Mai University between December 2004 and December 2006 were prospectively identified as having no surgical clips within the lumpectomy cavity. All patients underwent both US evaluation of the depth of tumour bed (D1) and radiographic evaluation of the depth of the anterior border of the pectoralis muscle (D2). These depth dimensions (D1 and D2) were compared using a paired t-test. The correlation of both methods was analyzed by Pearson correlation test. RESULTS: Depth dimensions by US were shorter than the radiographic film method in 85% of patients. The absolute mean difference of the depth (radiographic films minus US) was 0.129 cm. A paired t-test demonstrated that the difference between these two methods to be not statistically significant (p= 0.27). The absolute difference of depth between the two methods ranged from 0 to 0.5 cm. A significant correlation was found between US and radiographic film measurements (p<0.01). CONCLUSION: Plane radiographic film evaluation of the anterior border of the pectoralis muscle can be used to define the depth of the tumour bed in patients who have no surgical clips. However, the plane radiographic film method determines only the depth, not the transverse and longitudinal dimensions of the tumour bed. Additional information from US is needed to delineate the target volume for the tumour bed boost. In the absence of surgical clips, the authors recommend integration of both methods in breast boost planning process.