Mayumi Kaneko

Expression and localization of Reg IV in human neoplastic and non-neoplastic tissues: Reg IV expression is associated with intestinal and neuroendocrine differentiation in gastric adenocarcinoma.

Regenerating islet‐derived family, member 4 (Reg IV) is a candidate marker for cancer and inflammatory bowel disease. In the present study, immunohistochemical analysis of Reg IV was performed in various human neoplastic (n = 289) and non‐neoplastic tissues. In the stomach, foveolar epithelium was negative for Reg IV, whereas goblet cells of intestinal metaplasia and neuroendocrine cells at the base of intestinal metaplasia expressed Reg IV. Neuroendocrine cells of the small intestine and colon showed strong expression of Reg IV, whereas goblet cells of the small intestine and colon showed weak or no expression of Reg IV. Insulin‐producing beta cells of the endocrine pancreas were positive for Reg IV. Among 143 gastric adenocarcinomas, Reg IV expression was detected in 42 (29.4%) and was associated with both the intestinal mucin phenotype and neuroendocrine differentiation. No association was found between Reg IV expression and clinical characteristics such as tumour stage and patient prognosis. Of 36 colorectal adenocarcinomas, 13 (36.1%) were positive for Reg IV, which was associated with tumour stage (p = 0.0379, Fishers exact test). Expression of Reg IV was detected in 14 (93.3%) of 15 colorectal carcinoid tumours. Reg IV expression was also detected in 5 (21.7%) of 23 ductal adenocarcinomas of the pancreas. In contrast, lung cancers (n = 30) and breast cancers (n = 30) did not express Reg IV. This is the first immunohistochemical analysis of the expression and distribution of Reg IV protein in human tumours. These data suggest that Reg IV is expressed by gastrointestinal and pancreatic tumours, including adenocarcinomas and carcinoid tumours, and that Reg IV is associated with intestinal and neuroendocrine differentiation of the stomach and gastric carcinoma. Copyright

Significance of α9β1 and αvβ6 integrin expression in breast carcinoma

BackgroundBoth α9β1 and αvβ6 integrins have been newly identified from the tracheal epithelium of guinea pig. It has been pointed out that α9β1 functions as a receptor for tenascin-C and osteopontin. As for the ligands of αvβ6, fibronectin and tenascin-C have been identified. It has not been ascertained whether α9β1 and αvβ6 are expressed in normal breast tissue, benign breast lesion or breast carcinoma.MethodsImmunohistochemical staining for α9β1 and αvβ6 was performed in benign breast lesion and breast carcinoma specimens. Western blotting was carried out on 11 breast carcinoma cases.Resultsα9β1 was expressed in the cytoplasm of carcinoma cells in 23 of 90 cases (26%) and αvβ6 in the membrane of carcinoma cells in 16 of 90 cases (18%). However, these findings of α9β1 and αvβ6 did not correlate with any clinicopathological factors including the patients’ age, tumor size, histological type of carcinoma, location of carcinoma cells and hormone receptor status. With regard to the histological grade of carcinoma, αvβ6 and α9β1 expression did not statistically correlate, although no expression of αvβ6 was observed in 14 cases of Grade I. On Western-blott analysis strong and weak bands consistent with αvβ6 were noted in the membrane fraction extracted from breast carcinoma cells. On the other hand weak bands consistent with α9 subunit were noted in the whole cell lysates of breast carcinoma cells and very weak or no bands consistent with α9 subunit were noted in the membrane fraction extracted from the breast carcinoma cells.ConclusionsSignificance of α9β1 and αvβ6 integrins expression in breast carcinoma was still unknown on clinicopathological examination. The findings of Western blot analysis may indicate that the transportation system of glycoproteins such as integrins to the cell membrane of carcinoma cells is disturbed, although these integrins can be produced.

Cytokines facilitate chemotactic motility of breast carcinoma cells

BackgroundBoth growth and motility of various tumor cells have been shown to be influenced by surrounding cells such as lymphocytes, histiocytes and fibroblasts through various cytokines, growth factors and extracellular matrices. The role of cytokines and extracellular matrices produced by lymphocytes, histiocytes and fibroblasts on migration and invasion of breast carcinoma cells has not been fully investigated.MethodsWe investigated the effect of hepatocyte growth factor (HGF), interleukin (IL)-6, IL-8, IL-11, soluble type IV collagen and soluble laminin on the migration of 3 human breast carcinoma cell lines, MDA-MB-231, MCF-7 and T-47D, using a cell culture insert and a biocoat matrigel invasion chamber to assess migration across a matrigel-coated polyethylene telephtalate membrane.ResultsHGF, IL-6, IL-11 and IL-8 induced significant migration of MDA-MB-231 cells depending on the dose of each cytokine. However, type IV collagen and laminin inhibited migration of MDA-MB-231 cells. In contrast, IL-8 inhibited migration of MCF-7 cells and IL-6 induced significant migration of T-47D cells, while no other cytokine or extracellular matrix induced significant migration of MCF-7 and T-47D cells. Only HGF induced significant invasion of MDA-MB-231 cells depending on the dose. MCF-7 and T-47D cells did not invade in response to any of the cytokines and extracellular matrices tested.ConclusionsThese results suggest the possibility that the potency of chemotaxis or chemoinvasion differs according to the breast carcinoma cell line and that various cytokines and extracellular matrices secreted by lymphocytes, histiocytes and fibroblasts in the stroma of breast carcinoma can affect the invasion of breast carcinoma cells.

Value of immunohistochemistry in the differential diagnosis of pleural sarcomatoid mesothelioma from lung sarcomatoid carcinoma

Aims:  The differential diagnosis of pleural sarcomatoid mesothelioma (SM) from lung sarcomatoid carcinoma (LSC) invading parietal pleura and chest wall is a challenging issue. The aim of this study was to identify useful antibodies that can be used for the differential diagnosis of pleural SM from LSC.

Expression of vascular endothelial growth factor-C and its receptor in invasive micropapillary carcinoma of the breast.

Invasion to lymphatic vessels and metastasis to lymph nodes are frequent complications in invasive micropapillary carcinoma (IMPC) of human breast cancer. Vascular endothelial growth factor‐C (VEGF‐C) and its receptor, VEGFR‐3 have been implicated as the important factors in the formation of lymphatic vessels and recent experimental evidence strongly suggests that lymphangiogenesis in tumor promotes lymphatic metastasis. To clarify the mechanism of its occurrence, the expression of VEGF‐C, VEGFR‐3 and lymphatic vessel density (LVD) was examined in 40 cases of IMPC (pure and mixed type) and in 40 cases of pseudo‐IMPC. Cytoplasmic expression of VEGF‐C and VEGFR‐3 were more frequent in tumor cells of IMPC compared to those of pseudo‐IMPC. A significant positive correlation was found between the expression of VEGF‐C and VEGFR‐3 in both IMPC and pseudo‐IMPC. The expression of VEGF‐C was also significantly associated with higher peritumoral LVD, lymphatic invasion and number of lymph node metastasis in IMPC. These findings suggest that VEGF‐C promotes the proliferation of peritumoral lymphatic vessels and that lymphatic invasion and metastasis to lymph nodes are frequently induced in IMPC of breast.

Esophageal carcinosarcoma with basaloid squamous carcinoma and rhabdomyosarcoma components with TP53 mutation

Carcinosarcoma of the esophagus is a rare tumor with a distinct pathological entity having squamous cell carcinoma as the most described carcinomatous component. This paper reports the first case of carcinosarcoma of the esophagus that showed predominant basaloid squamous carcinoma component in addition to squamous cell carcinoma and poorly differentiated carcinoma and sarcoma component. A 64‐year‐old male patient consulted for dysphasia and chest pain was examined and found to have gastrointestinal fiber‐endoscope and a polypoid growth in the lower third of the esophagus. Partial esophagectomy was performed and the excised tumor showed histological features of carcinosarcoma with heterogeneous carcinomatous components with dominance of basaloid squamous carcinoma and minority of squamous cell carcinoma, poorly differentiated carcinoma, and sarcomatous component, immunohistochemically proven to be rhabdomyosarcoma. Immunohistochemical study and TP53 mutation analysis was carried out to explain the histogenesis of this rare tumor. The distinct immunohistochemical profiles of the carcinomatous and sarcomatous components suggested the possibility of transition from a carcinomatous to a sarcomatous component. The similar TP53 mutation in the carcinomatous and sarcomatous component suggested each of these components had the same origin, that is, the tumor was monoclonal in origin.

Meningioma in mature cystic teratoma of the ovary

A case of meningioma arising in a mature cystic teratoma of the ovary in a 60‐year‐old woman is described. The tumor was located in the right ovary, and salpingo‐oophorectomy was performed. The right ovary was 10 × 10 × 8 cm in size and contained an unilocular cyst. In the wall, a solid nodule measuring 3 × 3 × 2 cm was noted. Histologically, the cyst wall was composed of typical mature cystic teratoma. In contrast, the mural nodule was composed of the proliferating spindle‐ and polygonal‐shaped cells showing positive staining for epithelial membrane antigen and microcystic change was prominent. These findings were consistent with microcystic meningioma. The arachnoidal cells around mature brain tissue may be the origin of this unusual tumor. To the best of our knowledge, this is the first case of mature cystic teratoma with meningioma of the ovary reported in English medical literature. This case may further indicate the totipotential nature of mature cystic teratoma.

Case of clear cell ependymoma of medulla oblongata : Clinicopathological and immunohistochemical study with literature review

Clear cell ependymoma has been included in the WHO classification of the central nervous system in 1993, after the first report by Kawano et al. Since then, only a few cases have been reported. Most clear cell ependymoma cases reported in the literature so far were located in the supra‐tentorial compartment and/or cerebellum, and one case was in the cervical spinal cord. We report a case of clear cell ependymoma whose histological features were sufficient for the diagnosis and was unusually located in the fourth ventricle originating from the medulla oblongata. The tumor showed uniform tumor cells with perinuclear halo, nuclei being centrally located. Most of the tumor cells were arranged as perivascular pseudorosettes, and no ependymal canals or rosettes were evident. Mitotic figures were not frequent. Immunohistochemically, the tumor cells were strongly reactive for glial fibrillary acidic protein and vimentin, and weak and dot‐like positive for epithelial membrane antigen. Clear cell change of the tumor cells appeared to be fixation artifact because this feature was not evident in the frozen section.

Myxopapillary ependymoma with anaplastic features

A case of myxopapillary ependymoma with anaplastic features in 15‐year‐old boy is reported. The tumor was located in the intradural space extending to the 12th thoracic to 2nd lumbar vertebral level. It was excised with the accompanying spinal arch of the T12 to L2 vertebra. At operation, the tumor was not attached to the surrounding soft and bony tissues. The tumor, measuring 49 × 19 × 15 mm, was brownish‐yellow in color and involved the conus medullaris and filum terminale. Histologically, the tumor was composed of biphasic features of a hypercellular papillary growth area and a hypocellular myxoid area. In the papillary growth area, ependymal rosettes and perivascular pseudorosettes were observed.  These  findings  were  consistent  with  those of a myxopapillary ependymoma, although multiple foci of punctate necrosis within the tumor and proliferation of endothelial cells showing glomeruloid structures were observed. Many mitotic figures were also observed. In addition, the Ki‐67 labeling index of tumor cells was 10.1%. These findings are unusual for myxopapillary ependymoma, and therefore, it appeared that the diagnosis of myxopapillary ependymoma with anaplastic features was appropriate.

Loss of CD9 with expression of CD31 and VEGF in breast carcinoma, as predictive factors of lymph node metastasis

Immunohistochemical staining for CD9, CD31 and vascular endothelial growth factor (VEGF) was performed in breast carcinoma specimens. CD9 was expressed in the membrane of carcinoma cells in 61 of 93 cases (67%), CD31 in the membrane of carcinoma cells in 23 of 86 cases (27%), and VEGF in the cytoplasm of carcinoma cells in 26 of 86 cases (30%). The expression of CD9, CD31 and VEGF did not singly correlate with any clinicopathological factors. However, a loss of CD9 with concurrent expression of CD31 or VEGF in the invasive component showed a slight correlation with lymph node metastasis. These findings suggest that the potential for metastatic spread to lymph nodes in breast carcinoma may be synergically affected by various factors.