To de®ne genes that are essential to the initiation and progression of breast cancer we utilized subtractive hybridization and dierential display cloning techniques and isolated over 950 cDNAs from breast cell-lines derived from matched normal and tumor tissue. Of these, 102 cDNAs were characterized by DNA sequencing and Northern blot analysis. GenBank searches showed that one of these genes, T1A12 is identical to mac25, an insulin-like growth factor-binding protein related gene. Antibodies generated against the C-terminal region of the T1A12/mac25 protein were used to investigate its expression in 60 primary breast tissues. Sections of 12 benign, 16 ductal carcinoma in situ and 32 in®ltrating ductal carcinoma specimens were examined. Strong immunoperoxidase staining was observed in luminal epithelial cells of normal lobules and ducts, in apocrine cells of cysts and ®broadenomas. Moderate to weak protein expression was found in hyperplastic and DCIS cells, but no speci®c staining was detected in invasive carcinoma cells. FISH mapping using a PAC clone localized the T1A12/mac25 gene to 4q12-13. Microsatellite length polymorphism was studied using markers for 4q in paired normal and tumor breast tissues. Thirtythree per cent (10/30) of the samples were found to be polymorphic with D4S189 and D4S231 microsatellite markers and LOH was detected in 50% (5/10) of these informative samples. Our data indicate that T1A12/ mac25 expression is abrogated during breast cancer progression concomitant with loss of heterozygosity on chromosome 4q. T1A12/mac25 may therefore have a tumor suppressor-like function and its expression could indicate a disease with a more favorable status, having a better prognosis.

ABSTRACT. A patient presented with a 2 cm lump in the lower outer quadrant of the left breast. Mammogram and ultrasonography showed a solid mass with a microlobulated contour, partially irregular border and microcalcifications. MRI showed an irregular mass with early enhancement and high signal intensity, and the late-phase image demonstrated a partial washout pattern. These findings suggest that the tumour was a malignant invasive carcinoma. Non-invasive ductal carcinoma was diagnosed after a fine needle aspiration and core needle biopsy followed by a partial breast excision and sentinel lymph node (SLN) biopsy. A pathological examination of the lesion displayed characteristic small monomorphic cells, solid proliferation and massive distension within the lobular unit. The tumour was immunohistochemically negative for E-cadherin and pure lobular carcinoma in situ (LCIS) was diagnosed. Pure LCIS is very rare and there have been no previous reports of pure LCIS forming a solid mass. In 1999, Frykberg reported lobular carcinoma in situ (LCIS) was found in 1.3% of all breast malignancies [1]. LCIS was historically thought to lack any corollary signs of mass or calcification on mammography [1-3]); however, recent studies indicate that LCIS foci can be detected on mammograms with associated calcifications [4][5][6]. Histologically, the lesions frequently show multifocal LCIS in a background of atypical lobular hyperplasia, ductal carcinoma in situ and/or invasive carcinoma. Admittedly, pure LCIS is rare and there have been no previous reports of pure LCIS forming a solid mass. Here we report a case of pure LCIS presenting as a 20 mm solid mass detected by mammography, ultrasonography and MRI. Case reportThe patient was a 64-year-old female whose screening mammograms revealed a solid mass in the left breast. A physical examination revealed a hard mass of almost 2 cm in diameter, but there was no evidence of abnormal nipple discharge, skin changes or axillary lymphadenopathy. A mammogram demonstrated a high-density mass with a microlobulated contour, partially irregular margins and microcalcifications. The mass was located in the lower outside quadrant of the left breast, and was scored as breast imaging reporting and date system (BI-RADS) Category 4 (Figure 1). An ultrasonographic evaluation showed a lobulated, non-homogenous internal echo, an irregular border and highly echogenic spots (Figure 2). The MRI showed a lobulated mass 20 mm in diameter with early enhancement high signal intensity and a washout pattern in the late-phase image, which suggested that the tumour was a malignant invasive carcinoma (Figure 3). A fine needle aspiration and core needle biopsy were performed, and non-invasive ductal carcinoma was diagnosed.Subsequently, the patient underwent a breast partial resection and sentinel lymph node (SLN) biopsy. Complete dissection of the axillary lymph nodes was not performed because no metastasis was found in the SLN. Macroscopically, a whitish nodular mass measuring approximately 27 6 15 mm in diameter w...