ABSTRACT: Estrogen receptor (ER) and human epidermal growth factor 2 (HER2) are well-investigated molecules and the focus of many breast cancer therapies. There is a group of breast cancers lacking ER and HER2, but it is not fully understood. Treatment for these patients is limited to cytotoxic chemotherapy. The purpose of present study is to examine ER(-)/HER2(-) breast cancers, with a particular focus on epidermal growth factor receptor (EGFR). EGFR is a target molecule for which novel medicines have been recently developed for other organ cancers, however biological significance in breast cancer is not yet well demonstrated. Breast cancer specimens (n=58) were categorized into four groups: i) ER(+)/HER2(-) (51.7%); ii) ER(+)/HER2(+) (8.6%); iii) ER(-)/HER2(+) (20.7%); and iv) ER(-)/HER2(-) (19.0%). They were immunohistochemically (IHC) examined using antibodies for EGFR, platelet derived growth factor receptor (PDGFR)alpha, PDGFRbeta, parathyroid hormone (PTH) receptor, Ki-67, cyclinD1, p53, and vimentin. The Ki-67 labeling index (LI) was highest in ER(-)/HER2(-) (36.5%), and decreased in order from ER(-)/HER2(+) (31.4%), ER(+)/HER2(+) (17.7%), to (ER(+)/HER2(-) (15.9%) (p=0.001). EGFR, p53 and vimentin were highly expressed in ER(-)/HER2(-) breast cancer cells (p<0.01). CyclinD1 was inversely expressed to Ki-67 LI (p<0.001). Gene amplification of EGFR was examined by two in situ hybridization techniques, fluorescence in situ hybridization (FISH) and chromogenic in situ hybridization (CISH) in serial sections to IHC. Only 1 of 14 EGFR-positive breast cancers showed gene amplification at low levels by CISH. Overall, the ER(-)/HER2(-) breast cancer showed the highest Ki-67 LI, the most frequent expression of EGFR, p53 and vimentin, as well as the lowest expression of cyclinD1. It is unlikely that gene amplification contributes to EGFR expression. ER(-)/HER2(-) breast cancers have potential in the development of novel therapeutics, including targeted medicines.
Oncology Reports 09/2005; 14(2):337-43. · 1.84 Impact Factor
ABSTRACT: The surface pit pattern of early stage colorectal cancer changes with tumor growth and invasion. It was postulated by us that the expression of matrix metalloproteinase-7 is related to tumor invasiveness and disturbance of the pit pattern.
Sixty-eight colorectal epithelial tumors were examined, and the pit pattern was classified by stereoscopic microscopy. Immunostaining for matrix metalloproteinase-7 and its substrate laminin were performed.
The rate of matrix metalloproteinase-7 positive staining was significantly higher for mucosal (70.6%) and submucosal cancer (80.0%) than for adenoma (18.6%) (p<0.0083). The rate of matrix metalloproteinase-7 positive specimens was significantly higher for type IV and type V compared with type III pit patterns. Where the tumor surface was positive for matrix metalloproteinase-7, expression of laminin was negative in 40% of specimens with a type IV pit pattern and 100% of those with the type V pit pattern.
The results of this study indicate that expression of matrix metalloproteinase-7 is related to both the invasiveness of colorectal epithelial tumors and the disturbance of the pit pattern on the tumor surface.
Gastrointestinal Endoscopy 03/2004; 59(3):385-92. · 4.88 Impact Factor
ABSTRACT: Matrix metalloproteinase-7 (MMP-7), a proteolytic enzyme, is suspected to play an important role in the progression of various cancers. To clarify the clinical importance of MMP-7, we retrospectively analyzed MMP-7 expression in gastric epithelial tumors.
We tested 201 lesions (from 172 patients) of surgically or endoscopically resected gastric epithelial tumors (gastric cancer, 158 lesions; gastric adenoma, 32 lesions; hyperplastic polyp, 11 lesions). MMP-7 expression was immunohistochemically examined. Sections with immunostaining signals in more than 30% of tumor cells were judged to show positive expression.
MMP-7 was expressed in 33.3% (67/201) of all lesions. MMP-7-positive tumors were significantly more frequent in diffuse-type adenocarcinomas (62.2%; 28/45) compared with intestinal-type lesions (31.9%; 36/113; P < 0.001). Cancers invading the submucosa or deeper (60.5%; 46/76) were showed positivity significantly more frequently than mucosal cancers (22.0%; 18/82; P < 0.001). MMP-7-positive lesions increased with the progression of gastric epithelial tumors, including adenomas, mucosal cancers, and cancers invading the submucosal layer or deeper (P < 0.001). MMP-7 expression occurred significantly more often in lymphatic invasion-positive cancers (65.1%; 41/63) than in lymphatic invasion-negative cancers (24.2%; 23/95; P < 0.001).
The MMP-7-positive rate increased with the progression of gastric epithelial tumors, such as adenoma, mucosal cancer, and cancer invading the submucosal layer or deeper. MMP-7 was significantly associated with aggressive pathological phenotypes of cancer. The detection of the MMP-7 protein may be useful in pretherapeutic diagnosis.
Journal of Gastroenterology 01/2004; 39(5):434-40. · 4.16 Impact Factor