Abnormal expression of E-cadherin and beta-catenin may be a molecular marker of submucosal invasion and lymph node metastasis in early gastric cancer.

BACKGROUND: Impaired expression of E-cadherin and alpha- and beta-catenin is frequently observed in several human cancers. The aim of this study was to examine immunohistochemical expression of these adhesion molecules, focusing on early gastric carcinomas, and to investigate differences between differentiated and undifferentiated gastric cancer at the early phase of carcinogenesis. METHODS: Immunohistochemical staining of E-cadherin and alpha- and beta-catenin was performed using specimens from 143 patients with early gastric cancer. RESULTS: Abnormal E-cadherin and beta-catenin staining correlated with depth of tumour invasion in differentiated-type tumours. In contrast, abnormal staining was frequently found even in intramucosal carcinoma of undifferentiated-type tumours, suggesting an apparent difference in the onset of E-cadherin-catenin complex abnormality between the two cancer types. Absent staining of beta-catenin was associated with lymph node metastasis. Multivariate analysis revealed abnormal E-cadherin expression as an independent factor that correlated with submucosal invasion in early gastric cancer. CONCLUSION: Abnormal E-cadherin expression is a possible marker of submucosal invasion in differentiated-type early gastric cancer and absent beta-catenin staining could be used as a predictor of lymph node metastasis in both types.

Combined evaluation of NGF and p75NGFR expression is a biomarker for predicting prognosis in human invasive ductal breast carcinoma.

Nerve growth factor (NGF) is a member of the neurotrophin family and is essential for the differentiation and maintenance of neural cells. Recently, it has been reported that NGF is involved in the growth of breast cancer. On the other hand, two types of NGF receptors have been identified, a low-affinity receptor, p75NGFR, and a high-affinity receptor, TrkA. NGF-p75NGFR interaction is known to play an important role in apoptosis, whereas NGF-TrkA interaction is responsible for the survival of neural cells. We examined the relationship between clinicopathological factors, Ki-67 index, apoptotic index and the immunohistochemical expression of NGF, TrkA and p75NGFR in 71 invasive ductal breast carcinoma (IDBC) specimens. Our data indicate that positive Ki-67 expression (a labeling index exceeding 30%) correlates significantly with the positive expression of NGF (p=0.0091). Moreover, the apoptotic index was found to correlate with a strong expression of p75NGFR. Furthermore, patients who were NGF positive and p75NGFR negative had significantly poorer disease-free survival rates (p=0.0165). In contrast, those who were NGF negative and p75NGFR positive had significantly more favorable outcomes (p=0.0191). These findings suggest that a combined evaluation of NGF and p75NGFR expression is a predictive factor in the prognosis of IDBC patients.

Composite glandular-endocrine cell carcinoma of the common bile duct.

A rare case of composite glandular-endocrine cell carcinoma of the common bile duct is presented. Histologically, this tumor consisted of adenocarcinoma and small-cell neuroendocrine carcinoma, with a transition between the two components. The two distinct areas of the tumor were immunohistochemically different, whereas the transitional zone exhibited characteristics of both areas. These features suggest that the tumor arose from a multipotential stem cell. Although it has been reported that the presence of neuroendocrine differentiation in carcinomas indicates a poor prognosis, the patient in the present case was well at the time of writing this report. This may be due to the fact that adenocarcinoma, which characteristically has a low proliferative activity, constituted the majority of the tumor.

Expression of the hepatocyte growth factor/c-Met pathway is increased at the cancer front in breast carcinoma.

Expression of hepatocyte growth factor (HGF) and c-Met (HGF receptor) has been reported in many neoplasms. We investigated coexpression of HGF and c-Met to determine the role of the HGF/c-Met pathway in breast carcinoma, especially at the cancer front. Eighty-eight cases of carcinoma of the breast were studied by immunohistochemistry and by in situ hybridization for HGF and c-Met expression. The staining pattern was termed "front accentuation pattern" when it was most conspicuous at the cancer front. HGF and c-Met proteins were expressed in cancer and stromal cells, with autocrine and paracrine patterns. The front accentuation pattern of c-Met was observed in cancer cells, but not in stromal cells. The front accentuation pattern was not observed in HGF. Coexpression of HGF and c-Met at the cancer front was correlated with histologic grade, reduced patient survival and a high Ki-67 labeling index. Our findings suggest that the HGF/c-Met pathway acts primarily as a mitogen, especially at the cancer front, in a paracrine manner and affects some clinical factors, including patient survival.

Expression of Trk tyrosine kinase receptor is a biologic marker for cell proliferation and perineural invasion of human pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a widely known severe malignancy with a poor prognosis. Perineural invasion extending to the extra-pancreatic nerve plexus, a significant concern in the treatment is frequently present in this cancer. We analyzed immunohistochemical expression of neurotrophins (NGF, BDNF, NT-3) and the cognate receptors, Trk tyrosine kinase receptor family (TrkA, B, C) and p75NGFR in 28 surgically resected PDAC specimens. A comparative study between several clinicopathologic factors and Trk receptors revealed a significant correlation between increased expression of TrkA and cancer proliferation, as well as TrkC and cancer invasion, including venous and perineural invasion. The present findings revealed a novel mechanism in PDAC progression that is mediated via a NTs-Trk interaction.

Breast masses with peripheral rim enhancement on dynamic contrast-enhanced MR images: correlation of MR findings with histologic features and expression of growth factors.

PURPOSE: To investigate the histologic bases of rim enhancement of breast masses demonstrated on dynamic contrast material-enhanced magnetic resonance (MR) images. MATERIALS AND METHODS: Dynamic MR images of breast lesions (invasive carcinoma, n = 29; other, n = 6) in 35 women were reviewed. In each patient, subtraction images of the dynamic contrast-enhanced study were obtained, and early and delayed rim enhancement and delayed internal enhancement were evaluated. The MR findings were correlated with the ratio of microvessel density of the peripheral to the central portion of the lesion, fibrosis, and other histologic features, including expression of vascular endothelial growth factor (VEGF) and transforming growth factor ss1. RESULTS: Early rim enhancement was observed in 29% and delayed rim enhancement was noted in 60% of all patients. Small cancer nests, a high ratio of peripheral-to-central microvessel density, peripheral VEGF expression, and a low ratio of peripheral-to-central fibrosis were correlated with early rim enhancement. Delayed rim enhancement was correlated with a high degree of fibrosis and inflammatory changes. Delayed internal enhancement was correlated with a high degree of fibrosis. CONCLUSION: Rim enhancement of breast lesions at MR imaging is due to a combination of angiogenesis, distribution and degree of fibrosis, expression pattern of VEGF, and various histologic features.

Laparoscopic splenectomy for a giant splenic epidermoid cyst: report of a case.

The use of laparoscopic splenectomy has increased in recent years, primarily for patients with idiopathic thrombocytopenic purpura (ITP). We describe herein the first known case of a laparoscopic splenectomy to be performed in Japan for a patient with a giant splenic epidermoid cyst. A 26-year-old woman presented to our hospital with the major complaint of a feeling of abdominal fullness. Prior to surgery, an ultrasound-guided splenic cyst puncture was conducted for diagnostic purposes as well as to reduce the size of the cyst. The carbohydrate antigen 19-9 (CA 19-9) level was found to be elevated in the cystic contents and in the serum. Under laparoscopic guidance, the splenic vessels were ligated using a device for extracorporeal ligation, then divided. After the resected spleen had been placed in a retrieval bag, it was delivered out of the abdominal cavity without fragmentation. Following surgery, the patient's serum CA 19-9 level returned to normal. Splenic epidermoid cysts are most often encountered in young women, and laparoscopic surgery to remove cysts of this type is both minimally invasive and excellent from a cosmetic standpoint. Thus, laparoscopic surgery should be considered as the method of choice for the majority of patients diagnosed with a splenic epidermoid cyst.

Localization of vascular endothelial growth factor in synovial membrane mast cells: examination with "multi-labelling subtraction immunostaining".

Mast cells are believed to play a novel part in the development of destructive synovial pannus in rheumatoid arthritis (RA). This study was undertaken to investigate the localization of vascular endothelial growth factor (VEGF) in the synovial membrane using a unique immunostaining technique. Synovial specimens of RA patients were examined immunohistochemically and were compared with specimens from non-RA controls. Multi-labelling subtraction immunostaining, a modification of double- and triple-labelling immunostaining, revealed that the VEGF-positive cells were identical to tryptase-positive cells (mast cells). No other cell types were found to be positive for VEGF. The synovium of RA patients showed a larger number of VEGF-positive mast cells than that of non-RA controls (P<0.001). The study suggests that mast cell-derived VEGF may contribute to the development of synovial pannus in RA.