Pregnancy-specific glycoprotein expression in normal gastrointestinal tract and in tumors detected with novel monoclonal antibodies.

Pregnancy-specific glycoproteins (PSGs) are immunoglobulin superfamily members related to the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family and are encoded by 10 genes in the human. They are secreted at high levels by placental syncytiotrophoblast into maternal blood during pregnancy, and are implicated in immunoregulation, thromboregulation, and angiogenesis. To determine whether PSGs are expressed in tumors, we characterized 16 novel monoclonal antibodies to human PSG1 and used 2 that do not cross-react with CEACAMs to study PSG expression in tumors and in the gastrointestinal (GI) tract using tissue arrays and immunohistochemistry. Staining was frequently observed in primary squamous cell carcinomas and colonic adenocarcinomas and was correlated with the degree of tumor differentiation, being largely absent from metastatic samples. Staining was also observed in normal oesophageal and colonic epithelium. PSG expression in the human and mouse GI tract was confirmed using quantitative RT-PCR. However, mRNA expression was several orders of magnitude lower in the GI tract compared to placenta. Our results identify a non-placental site of PSG expression in the gut and associated tumors, with implications for determining whether PSGs have a role in tumor progression, and utility as tumor biomarkers.

Prevalence of bone marrow micrometastases in esophagogastric cancer patients with and without neoadjuvant chemoradiotherapy.

BACKGROUND: Bone marrow micrometastases are present in a high proportion of patients undergoing curative resection for esophagogastric cancer. The incorporation of preoperative systemic therapies into these patients' treatment is widely practiced. This study investigates the effect of neoadjuvant chemoradiotherapy (CRT) on the incidence of micrometastases and the viability of detected tumor cells. MATERIALS AND METHODS: Rib bone marrow was obtained from patients (n = 106) in three centers, who were selected for potentially curative resection. Patients received neoadjuvant CRT plus surgery (n = 55), or surgery alone (n = 51). To detect micrometastases, mononuclear cells were isolated from fresh marrow and immediately stained immunohistochemically with an anti-cytokeratin-18 antibody using the APAAP technique. Tumor cell viability was assessed by immunohistochemical staining of marrow cell cultures for cytokeratin-positive cells. RESULTS: Micrometastases were detected in fresh marrow in 42% (23/55) of patients who received neoadjuvant CRT plus surgery, and in 67% (34/51) of patients treated with surgery alone. Viable tumor cells were demonstrated in 10 of 18 marrow cultures from CRT plus surgery cases. In this patient subset, combination of results of staining fresh and cultured marrow significantly increased micromet detection to 78%. CONCLUSIONS: A significant proportion of patients with esophagogastric cancer have disseminated viable tumor cells at time of surgery, irrespective of pre-operative treatment. The use of marrow culture in parallel with fresh marrow staining may increase the detection of micrometastases. The persistence of tumor cells resistant to systemic therapy may explain why these regimens fail in a majority of patients.