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.

Paget's disease of the breast: clinical, imaging and pathologic findings: a review of 16 patients.

OBJECTIVES: To determine the clinical, imaging and pathological findings of Paget's disease of the breast. MATERIALS AND METHODS: Approval by Institutional Review Board was granted and informed consent was waived. Retrospective review of the pathological diagnosis of 2,361 women with breast carcinoma between January 2004 and April 2010 revealed 27 patients with Paget's disease of the breast. The clinical, mammographic and ultrasonographic images were retrospectively reviewed. RESULTS: The prevalence of Paget's disease of the breast was 1.14% of all breast carcinoma at this institution. Of the 27 patients with Paget's disease, only 16 had imaging studies and this group constituted the basis of this study. All 16 patients were women, with ages ranging from 36-68 years (mean age 50.31 years). Eleven patients presented with clinical findings suggestive of Paget's disease of the breast. Seven of these 11 patients also had associated palpable mass(es). Four patients presented with a palpable mass alone and one presented with bloody nipple discharge alone. Mammography was performed in all 16 patients and ultrasonography (US) in 15 patients. Of the 16 mammographic studies, two were negative. Of the 15 US studies, three were negative. Of these three negative US studies, two also had negative mammography and one had pleomorphic microcalcifications on mammogram. US was helpful in detecting multifocality in two patients. Mammography was 100% positive in patients who presented with palpable breast mass(es) and bloody nipple discharge, but 50% positive in patients who had clinically suggestive Paget's disease alone. Almost all patients (15/16) had underlying breast malignancies. Seven patients had multifocality or multicentricity. Modified radical mastectomy was performed in 13 patients, simple mastectomy in two, and wide local excision in one patient. Pathological findings were ductal carcinoma in situ (DCIS) (n = 3), invasive ductal carcinoma (IDC) (n = 10), metaplastic carcinoma (n = 1), invasive lobular carcinoma (ILC) (n = 1), and only Paget's disease of the nipple without underlying breast carcinoma (n = 1). CONCLUSION: Patients with Paget's disease of the breast have a high incidence of an underlying breast carcinoma. Most of the patients in this study presented late and were more likely to have positive mammograms. Mammography should be performed to identify the underlying breast carcinoma. Those who have only nipple areolar changes and no palpable mass have less positive mammography and less invasive carcinoma.

Breast calcifications: which are malignant?

Most calcifications depicted on mammograms are benign. However, calcifications are important because they can be the first and earliest sign of malignancy. For detection and analysis of microcalcifications, high-quality images and magnification views are required. The American College of Radiology (ACR) Breast Imaging Reporting and Data System (BI-RADS) classifies calcifications on mammograms into three categories: typical benign, intermediate concern and higher probability of malignancy, according to types and distribution of calcifications. Benign calcifications are typically larger, coarser, round with smooth margins and have a scattered or diffuse distribution. Malignant calcifications are typically grouped or clustered, pleomorphic, fine and with linear branching. It is important for radiologists to detect, evaluate, classify and provide appropriate recommendations for calcifications perceived on mammograms to provide proper management.

Atypical and suspicious categories in fine needle aspiration cytology of the breast: histological and mammographical correlation and clinical significance.

INTRODUCTION: This study aims to correlate fine-needle aspiration specimens diagnosed as C3 (atypical, probably benign) and C4 (suspicious, probably malignant) with histology and mammography, and to evaluate these two cytology categories in terms of diagnostic usefulness and patient management. METHODS: All fine-needle aspiration (FNA) specimens in categories C3 or C4 at the Maharaj Nakorn Chiang Mai Hospital, Thailand between 2000-2004 were reviewed. Results were correlated with available histological and mammographical studies. RESULTS: 148 FNA specimens were identified, comprising 43 category C3 and 105 category C4. Histology was available in 90 cases. 14 (64 percent) C3 cases showed benign histology on biopsy and eight (36 percent) were malignant. 13 (19 percent) C4 cases were benign on biopsy, whereas 55 (81 percent) were malignant. Mammographical studies were available in 56 of the histologically-proven cases. All seven cases with benign mammograms had benign histology, and all 26 cases called "highly suggestive of malignancy" were malignant on histology (five C3 and 21 C4). Of the 23 cases called "suspicious abnormality" on mammography, 14 turned out to be malignant on biopsy (one C3 and 13 C4). CONCLUSION: Our study supports maintaining cytology categories C3 and C4. About two-thirds of C3 cases were benign on biopsy whereas 81 percent of C4 cases were malignant (p-value is less than 0.001). There was complete correlation between histological and mammographical studies except those with equivocal mammograms. Our study supports the combined use of clinical, mammographical and cytological findings for optimal patient management. This is especially important for patients with C3 aspiration results, in order to avoid unnecessary surgery for benign lesions.