Reduced expression of epidermal growth factor receptor related protein in gastric cancer.

OBJECTIVES: The recently cloned epidermal growth factor receptor related protein (ERRP) has been proposed to be a negative regulator of the epidermal growth factor receptor (EGFR). Because of the causal involvement of EGFR and its ligands in gastric cancer growth, we investigated expression of ERRP and cell proliferation in human gastric cancer. METHODS: We examined ERRP expression and localisation in surgical specimens of gastric cancers from 47 patients versus non-malignant gastric mucosa and determined their relationship to cell proliferation and differentiation. We also examined expression of ERRP by western blotting in three different gastric cancer cell lines. To further determine the functional properties of ERRP, we examined the effect of ERRP on epidermal growth factor (EGF) induced EGFR phosphorylation essential for its activation in MKN-28 gastric cancer cells. RESULTS: ERRP expression was dramatically reduced in gastric cancers (34% of all specimens positive) compared with non-malignant gastric mucosa (66% of specimens positive). Expression of ERRP in cancer cells inversely correlated with cell proliferation and grade of malignancy. Cell lines derived from metastatic gastric cancers had reduced ERRP expression compared with cell lines derived from a non-metastatic cancer. Exogenous ERRP protein markedly inhibited EGF induced EGFR phosphorylation in gastric cancer cells providing a novel molecular mechanism of its action. CONCLUSIONS: Our data indicate that downregulation of ERRP could play an important role in gastric cancer differentiation and progression. ERRP is a negative regulator of tumour cell proliferation and may exert its inhibitory effect, in part, by attenuating EGFR activation.

Sarcomatoid carcinoma of the colon: a case report.

Sarcomatoid carcinoma is a rare biphasic tumor characterized by a combination of malignant epithelial and mesenchymal cells. We report a rare case of sarcomatoid carcinoma of the colon. A 41-yr-old woman was hospitalized with a history of melena. Total colectomy was performed under the impression of colonic carcinoma. Histologically, the tumor was composed of differentiated adenocarcinoma in superficial portion and sarcomatoid spindle cells in deeper portion with a transitional area between the two portions. The sarcomatous areas revealed polygonal and spindle-shaped anaplastic malignant cells arranged in sheet, short fascicular or haphazard pattern. Immunohistochemically, tumor cells showed a positive immunoreaction for cytokeratin, epithelial membrane antigen, and vimentin. The histopathological and immunohistochemical transitions between the adenocarcinoma area and the spindle cell area suggested that the sarcomatous elements originated from the adenocarcinoma during tumor progression.

Expression profile of nine novel genes differentially expressed in hepatitis B virus-associated hepatocellular carcinomas.

Chronic hepatitis B virus (HBV) infection is known to be one of the major causes in the development of hepatocellular carcinoma (HCC), although the biomolecular mechanism(s) involved remain unclear. To identify the cellular gene(s) involved in HBV-associated hepatocarcinogenesis, we used the mRNA differential display method and examined three paired tumor and nontumor tissues, all of which had chromosomally integrated HBV-DNA through chronic infection. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13-mers, genes decreased or increased in expression more than twofold between each tumor tissue and its paired nontumor tissue were identified. Twenty-nine known genes and four novel genes were differentially over-expressed in the HCC tumor tissues. In contrast, 27 known genes and five novel genes were under-expressed in those tumor tissues. The nucleotide sequences of the nine novel gene fragments were determined and their expression patterns were examined in 40 HCC samples. HA61T2, PT18, HG63T1, and HG57T1 were preferentially over-expressed in 32 cases (80%, P<0.001), 24 cases (60%), 23 cases (57.5%) and 22 cases (55%) of the 40 tumor tissues, respectively. There was an increased frequency of HG57T1 over-expression in HCC patients with HBV-positive serology and low serum alpha-feto protein (AFP) levels (P<0.05). DNT10, PT8, PT19, ENT25 and HA6T4 were under-expressed in 26 cases (65%), 23 cases (57.5%), 21 cases (53%), 20 cases (50%) and 18 cases (45%) of the 40 tumor samples, respectively. There was a strong correlation of DNT10 under-expression with high serum AFP level in HCC patients, irrespective of HBV serology (P<0.01). HA6T4 was preferentially under-expressed in HCC tumors in patients with HBV-positive serology and high serum AFP levels (P<0.05). Thus, the functional analyses of the known and novel genes identified in this study should prove valuable to further understand the mechanism(s) of hepatocarcinogenesis.

Establishment and characterization of chromosomal aberrations in human cholangiocarcinoma cell lines by cross-species color banding.

Cholangiocarcinoma (CC), a malignant neoplasm of the biliary epithelium, is usually fatal because of difficulty in early diagnosis and lack of availability of effective therapy. Furthermore, little is known about the genetics and biology of CC. Only a few reports concerning cytogenetic studies of CC have been published, and few cell lines have been established. We recently established four CC cell lines, designated as SCK, JCK, Cho-CK, and Choi-CK, and report the first application of cross-species color banding (RxFISH) and multiple chromosome painting for the characterization of the chromosomal rearrangements of these CC cell lines. Each cell line had unique modal karyotypic characteristics and showed a variable number of numerical and structural clonal cytogenetic aberrations. Chromosomes 3, 6, 7, 8, 12, 14, 17, and 18 were commonly involved in structural abnormalities. Homogeneously staining regions were determined in SCK and JCK, and double minute chromosomes were found in Cho-CK. The chromosomal aberrations of the four CC cell lines were effectively analyzed by RxFISH and FISH with multiple chromosome painting probes. The nonrandom rearrangements suggest candidate regions for isolation of genes related to CC.

A case of persistent endometriosis after total hysterectomy with both salpingo-oophorectomy managed by radiation therapy.

Persistent endometriosis after total hysterectomy and both salpingo-oophorectomy (TH with BSO) is a rare condition and the etiology is uncertain. The exact incidence of persistent endometriosis after definitive surgery is not known. In addition, the treatment of persistent endometriosis after complete surgical excision is controversial. We report a case of persistent endometriosis with vaginal and sigmoid-colonic invasion after TH with BSO. The lesions were not responsive to hormonal therapy. The patient was managed successfully by therapeutic pelvic radiation.

Pale bodies in hepatocellular carcinoma.

Histochemical, immunohistochemical and ultrastructural studies were performed on cases of hepatocellular carcinoma (HCC) with pale bodies (PB). HCC containing PBs was observed in 3 (5.5%) of 55 consecutively resected HCC cases. Histologically, a large number of hepatocytes displayed pale or eosinophilic staining of the cytoplasm, resulting in ground-glass appearance. They were aggregated in nodular pattern, or diffusely intermixed with other malignant hepatocytes. PBs were negative for periodic-acid Schiff and Masson's trichrome staining. The inclusions showed a strong positive reaction for fibrinogen and some of them were weakly positive for albumin but negative for hepatitis B surface antigen, hepatitis B core antigen, alpha-fetoprotein and alpha-1-antitrypsin. Ultrastructurally, PBs were membrane-bound and contained granular materials of moderate electron density, and were closely related to dilated rough endoplasmic reticulum. These findings support that PBs are secretory fibrinogen accumulated in cystic ER and that such intracellular accumulation possibly reflects a defective transport of fibrinogen.

Clinicopathologic and genotypic study of extranodal nasal-type natural killer/T-cell lymphoma and natural killer precursor lymphoma among Koreans.

BACKGROUND: This study aimed to define genotypic profile and to describe the clinicopathologic features of nasal-type natural killer (NK)/T-cell lymphoma of nasal and extranasal origin and NK precursor lymphoma. METHODS: NK/T-cell lymphomas from the upper aerodigestive tract (n = 45), skin (n = 2), gastrointestinal tract (n = 3), and soft tissue (n = 2) and NK precursor neoplasms (n = 3) were studied. Immunophenotype was analyzed by immunohistochemistry and flow cytometry. In situ hybridization with EBER 1/2 RNA probes was performed. T-Cell Receptor (TCR)-gamma gene rearrangement was analyzed by seminested polymerase chain reaction with heteroduplex analysis. Overall survival rate was correlated with clinicopathologic parameters and compared by Wilcoxon test. RESULTS: Clonal TCR-gamma gene rearrangement was detected in 3 of 31 upper aerodigestive and 1 of 2 skin tumors. When immunostained using paraffin embedded tissue, 6 upper aerodigestive lymphomas were negative for CD56 in which 4 cases lacked clonal TCR gene rearrangement. Epstein-Barr virus (EBV) mRNA was detected in 33 upper aerodigestive tumors including 26 of 29 nasal tumors (90%), and 7 of 10 extranasal tumors (70%). There was no histologic, immunophenotypic, or genotypic differences according to the lineage and EBV association in upper aerodigestive lymphomas. Among the patients with upper aerodigestive tumors, overall 1-year survival rate was 41%, and correlated well with the stage (P < 0.05) but not with the size of tumor cells, EBV status, and lineage (P > 0.05). Median survival rate of lymphomas from other sites excluding upper aerodigestive tract was not significantly different from that of upper aerodigestive lymphomas with same stage (P > 0.05). Unlike nasal-type NK/T-cell lymphomas, NK precursor lymphoma involved the bone marrow and lymph nodes at initial presentation or in the course of disease. Tumor cells were positive for TdT in all and myeloid markers in two. TCR gene rearrangement was germ line. CONCLUSIONS: Most upper aerodigestive nasal-type NK/T-cell lymphomas among Koreans are genotypically of NK derivation and few belong to T lineage. Presence or absence of EBV has no significant correlation with the histologic changes and the lineage of these lymphomas.

Pseudotumorous hyperplasia of the caudate lobe in the non-cirrhotic liver: MR and CT arterial portography appearance.

We describe the magnetic resonance image and computed tomographic arterial portography appearance of pseudotumorous hyperplasia in the caudate process of the caudate lobe in a non-cirrhotic patient. A prominent portal vein branch directly arising from the right main portal branch was seen in the center of the lesion on magnetic resonance imaging and computed tomographic arterial portography. We think that portal flow change of the caudate lobe by an anomalous portal branch may be correlated to pseudotumorous hyperplasia.

Diffuse hepatic hemangiomatosis in an adult.

Diffuse hepatic hemangiomatosis without extrahepatic lesions is extremely rare in adults. A case of diffuse hepatic hemangiomatosis involving right lobe in a 50-year-old woman was presented. The hemangiomatosis was demonstrated by ultrasonography, computerized tomography (CT) and magnetic resonance image (MRI), and was confirmed histopathologically. Although diffuse hepatic hemangiomatosis is a rare disease in adults, its diagnosis should be considered in patients with diffuse tumor growth in one or both hepatic lobes and distinguished from malignant tumors. The present case is the first documented case of diffuse hepatic hemangiomatosis in an adult in Korea.

Intravascular papillary endothelial hyperplasia in a vascular lesion of the paranasal sinus.

Intravascular papillary endothelial hyperplasia (IPEH) is usually a cutaneous lesion thought to represent a peculiar manifestation of an organizing thrombus. The principal significance of IPEH is its microscopic resemblance to angiosarcoma and possible misinterpretation as such. The occurrence of IPEH in the paranasal sinus is exceedingly rare. In this article, we report the first case to our knowledge of IPEH in a vascular lesion that originated from the ethmoid sinus and extended into the sphenoid sinus and sella. Despite the benign nature of this lesion, it could have been mistaken for a malignant tumor because of its clinical course and radiologic findings.

Early ultrastructural changes of apoptosis induced by fumonisin B1 in rat liver.

A time sequential study was performed to investigate the histological and ultrastructural findings of fumonisin B1-induced apoptosis in the male Sprague-Dawley rat liver. Six hours after administration of FB1, marked morphologic changes of hepatocytes included the appearance of small vacuoles along the margin of cell membrane. Twelve hours after injection of FB1, acidophilic degeneration of cells occurred, but no fragmented nucleus was evident around the centrilobular area, with few apoptotic cells. By electron microscope, the degenerated acidophilic cells revealed following changes: characteristic formation of cytoplasmic vacuoles, condensed cytoplasm, detachment from neighboring cells, and as well as margination of nuclear chromatin and swollen mitochondria with amorphous matrical deposit. The number of apoptotic cells or bodies was further enhanced at 24 hours in the vicinity of dense acidophilic cells, resulting in a marked increase over the values of control rats. Serum analysis revealed the elevation of cholesterol levels from the beginning to the end of this experiment. Morphologic data and serum findings in this study support the theory that FB1-induced alteration of membrane lipid constituents of the hepatocytes are likely to be early key events in explaining the FB1 apoptotic effect.

Radiological appearance of primary branchial cleft cyst carcinoma.

The hypothesis that primary branchiogenic carcinoma originates from a branchial cleft cyst is controversial. Many reports regarding primary branchiogenic carcinoma failed to provide sufficient evidence to distinguish it from metastatic cervical lymph nodes arising from previously unrecognized primary tumours. The radiological appearance of malignant transformation from a branchial cleft cyst has not been reported previously in the English literature. A radiological study is presented that confirms the primary branchiogenic carcinoma. The management in suspected cases would be wide surgical excision of the tumour including ipsilateral radical neck dissection followed by radiation therapy.

Ovarian sex cord tumor with annular tubules in a patient with Turner syndrome.

A case of ovarian sex cord tumor with annular tubules (SCTAT) in a 24-year old woman with Turner syndrome is presented. Close association of dysgenetic gonads and gonadoblastoma has been clearly documented, and there have been sporadic reports of patients with other gonadal tumors. To our knowledge, a case of SCTAT in a patient with 45,X/46,XX Turner syndrome has not been reported. On the basis of histopathologic, immunohistochemical, and ultrastructural findings, we suggest that the SCTAT originated from pluripotential stem cells of the gonads and differentiated into either granulosa cells or Sertoli cells. We postulate a possible relationship between the SCTAT and gonadoblastoma based on the morphologic resemblance and occurrence in dysgenetic gonads.