Molecular constitution of breast but not other reproductive tissues is rich in growth promoting molecules: a possible link to highest incidence of tumor growths.

In the current study we tested if highest incidence of benign as well as cancer growths in breast tissue is due to constitutive molecular composition of this tissue. To delineate the molecular basis, we compared the expression of nine functional gene modules (total 578 genes) that regulate major positive growth and negative inhibitory signals in normal breast with two other reproductive tissues, ovary and uterus. We present data to demonstrate that breast tissues constitutively have very highly elevated levels of several growth promoting molecules and diminished levels of inhibitory molecules which may, in part, contribute for highest incidence of tumor growths in this tissue.

Molecular risk assessment for breast cancer development in patients with ductal hyperplasias.

PURPOSE: It has been reported that approximately a million women are diagnosed with benign breast lesions that include ductal hyperplasias per year in the United States. Recent studies that followed women with benign lesions have established that about 8% to 9% of them will subsequently develop invasive breast cancer (IBC). However, currently, there are no means of identifying a subclass of "true precancerous tissues" in women with ductal hyperplasias who will subsequently develop cancer. The purpose of this study is to investigate whether expression of hyaluronoglucosaminidase 1 (HYAL1), a known tumor promoter, in hyperplastic tissues identifies a "true precancerous stage" and predicts subsequent IBC development. EXPERIMENTAL DESIGN: A retrospective study was conducted with archival benign tissues of various histologic types and clinical information on development/nondevelopment of IBC. The control group was hyperplastic tissues from women who had no prior history of IBC and did not develop cancer in 5 to 7 years after diagnosis (n = 81). The test group was hyperplastic tissues from patients who developed cancer (n = 82). HYAL1 expression was studied by immunohistochemistry, and the results were statistically analyzed for significant association to develop cancer (P value), specificity, sensitivity, positive predictive value, and negative predictive value. RESULTS: Statistical analysis of HYAL1 expression data showed very highly significant association between its expression and subsequent cancer development (P = 0) and very high sensitivity (0.83), specificity (0.84), positive predictive value (0.84), and negative predictive value (0.83). CONCLUSIONS: The expression of HYAL1 in ductal hyperplastic tissues is a strong predictor of subsequent development of IBC; therefore, it can be applied as a diagnostic marker either singly or in combination with other marker(s) to screen benign tissues to predict subsequent development of IBC. Detection at the precancerous stage and treatment could drastically cut down breast cancer incidence and deaths from it.

Synovial sarcoma of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 10 cases.

Only a few synovial sarcomas arising in the gastrointestinal tract have been reported, most of them are from the esophagus. We report clinical, histopathologic, and immunohistochemical features of 10 gastric synovial sarcomas. These tumors occurred in 4 males and 6 females with mean and median age of 52 years (range, 29 to 68 y). None of the patients had evidence of synovial sarcoma elsewhere. The tumor sizes ranged from 0.8 to 15 cm (mean, 3 cm). Two tumors were large transmural masses of 8 and 15 cm, and 8 were 0.8 to 6 cm, ulcerated cuplike or plaquelike or oval lesions predominantly involving the luminal side. Histologically, 9 tumors were monophasic one also having a poorly differentiated round cell component, and one was biphasic. Microscopic calcifications were present in 2 tumors. At least focal keratin (AE1/AE3 cocktail, keratin 7) and/or epithelial membrane antigen-positivity were detected in all tumors, and there was no CD34 or KIT-immunoreactivity. SYT-SSX fusion transcripts were demonstrated in 7 cases studied by a polymerase chain reaction-based fusion transcript assay. Five patients had a partial gastrectomy, and 5 underwent wedge or segmental resections. Two patients had received chemotherapy after surgery, but none had postoperative radiation. Four patients with plaquelike or cuplike tumors < or =3 cm were alive and well 1, 2, 2, and 18.5 years after surgery. Two patients died of tumor 25 and 29 months after surgery. One of them had a large 8-cm tumor, and another had a 2-cm tumor with a poorly differentiated component. Two patients were alive with recurrences 6 and 48 months after diagnosis. Synovial sarcoma rarely occurs as a gastric primary tumor. It has a variable prognosis depending on tumor size and differentiation, and should be considered in the differential diagnosis of KIT-negative gastric spindle cell neoplasms.

The Cell Surface Estrogen Receptor, G Protein- Coupled Receptor 30 (GPR30), is Markedly Down Regulated During Breast Tumorigenesis.

BACKGROUND: GPR30 is a cell surface estrogen receptor that has been shown to mediate a number of non-genomic rapid effects of estrogen and appear to balance the signaling of estrogen and growth factors. In addition, progestins appear to use GPR30 for their actions. Therefore, GPR30 could play a critical role in hormonal regulation of breast epithelial cell integrity. Deregulation of the events mediated by GPR30 could contribute to tumorigenesis. METHODS: To understand the role of GPR30 in the deregulation of estrogen signaling processes during breast carcinogenesis, we have undertaken this study to investigate its expression at mRNA levels in tumor tissues and their matched normal tissues. We compared its expression at mRNA levels by RT quantitative real-time PCR relative to GAPDH in ERα"-positive (n = 54) and ERα"-negative (n = 45) breast cancer tissues to their matched normal tissues. RESULTS: We report here, for the first time, that GPR30 mRNA levels were significantly down-regulated in cancer tissues in comparison with their matched normal tissues (p < 0.0001 by two sided paired t-test). The GPR30 expression levels were significantly lower in tumor tissues from patients (n = 29) who had lymph node metastasis in comparison with tumors from patients (n = 53) who were negative for lymph node metastasis (two sample t-test, p < 0.02), but no association was found with ERα, PR and other tumor characteristics. CONCLUSIONS: Down-regulation of GPR30 could contribute to breast tumorigenesis and lymph node metastasis.

Identification of MMP-1 as a putative breast cancer predictive marker by global gene expression analysis.

Breast cancer is the second leading cause of cancer death for women in the United States. In 2005, about 215,000 cases of invasive breast cancer (IBC) and 50,000 cases of ductal carcinoma in situ will be diagnosed and 40,000 women will die of IBC in the US. Yet there is presently no molecular marker that can be used to detect a precancerous state or identify which premalignant lesions will develop into invasive breast cancer. Here we report the gene expression analysis of atypical ductal hyperplastic tissues from patients with and without a history of breast cancer. We identify MMP-1 as a candidate marker that may be useful for identification of breast lesions that can develop into cancer.

Acute necrotizing esophagitis: a case report.

Acute necrotizing esophagitis is rare. The exact etiology is unknown in most cases. The esophagus appears black, necrotic and ulcerated on the upper endoscopy, thus the term "black esophagus" is used. Histologically, there is necrosis of the esophageal mucosa and submucosa. Here, we present a patient with cholangiocarcinoma who had upper gastrointestinal bleeding and was found to have acute necrotizing esophagitis on the upper endoscopy.