Eriko Miyazaki

Differential expression of CD34 in normal colorectal tissue, peritumoral inflammatory tissue, and tumour stroma

Aims—To investigate the role of CD34 positive stromal cells, namely dendritic interstitial cells, in the desmoplastic stroma formation of malignant epithelial neoplasms the distribution of CD34 positive stromal cells was examined in human colorectal adenocarcinomas, peritumoral inflammatory tissue, and normal tissue. Methods—Forty one surgically resected human colorectal adenocarcinomas and their corresponding peritumoral inflammatory and normal tissues were examined. To distinguish CD34 positive stromal cells from vascular endothelial cells, immunostaining for both CD34 and CD31 was performed. The distribution of myofibroblasts was also analysed immunohistochemically, and double staining with CD34 and α smooth muscle actin (ASMA) was performed. Results—Most of the stromal cells in the normal colorectal submucosa, muscularis propria, subserosa, and perirectal tissue were positive for CD34. In contrast, the peritumoral inflammatory tissue and the tumour stroma had no CD34 positive stromal cells. The distribution of myofibroblasts was almost the same as in the aforementioned series. No stromal cells double positive for CD34 and ASMA were detected in the peritumoral inflammatory tissues. Conclusions—Most stromal fibroblasts are CD34 positive stromal cells (dendritic interstitial cells). In colorectal adenocarcinomas, a lack of CD34 expression in stromal cells is associated with desmoplastic reaction.

Vinculin: Its Possible Use as a Marker of Normal Collecting Ducts and Renal Neoplasms with Collecting Duct System Phenotype

Vinculin is a cytoskeletal protein associated with membrane actin-filament-attachment sites of cell-cell and cell-matrix adherens-type junctions. In this article, we examine the expression of vinculin to elucidate its role in human renal neoplasms. We reviewed surgically resected specimens and selected available tissue from 79 renal tumors in 78 patients. There were 55 men and 23 women. Their mean age was 61 years and the mean size of the renal tumors was 6.1 cm. All renal tumors were examined by immunohistochemistry using a monoclonal antibody against vinculin. Overall, 17 (21.5%) renal tumor samples reacted with vinculin. The positive ratio in various types of renal tumors was as follows: conventional-type (clear cell), 0/54; papillary-type, 5/12; chromophobe-type, 5/5; sarcomatoid-type, 3/4; collecting duct carcinoma, 3/3; and oncocytoma, 1/1. The positive rate of conventional-type renal cell carcinomas (RCCs) is significantly different from that of other renal tumors (P < .01). Normal kidney, conventional, and papillary-type RCCs exhibited positive signals in Western blot analysis. These results suggest that vinculin may serve as a useful marker of renal neoplasms with collecting duct system phenotype such as chromophobe-type RCC.

Appearance of denuded hepatic stellate cells and their subsequent myofibroblast-like transformation during the early stage of biliary fibrosis in the rat

To investigate the early in vivo response of hepatic stellate cells in biliary fibrosis, we examined rat livers during the first 7 days after bile duct ligation using light microscopy, immunohistochemistry, electron microscopy, and immunoelectron microscopy. At day 1 after bile duct ligation, α-smooth muscle actin-positive fibroblasts appeared and then increased in number around the proliferating bile ductules. With time, the destruction of the external limiting plate became accentuated because of the invasion of the proliferating bile ductules and periductural fibrosis. At day 7, stromal cells containing fat droplets appeared in the fibrous tissue adjacent to the periportal parenchyma; these are termed denuded hepatic stellate cells. In the fibrous tissue disconnected from the liver parenchyma, the denuded hepatic stellate cells were replaced by myofibroblast-like cells. Meanwhile, the expression of transforming growth factor-β1 on biliary epithelial cells increased. These results indicate the dual origin of myofibroblasts in experimental biliary fibrosis, the periductural and periductal fibroblasts in the initial stage, and the denuded hepatic stellate cells in the subsequent stage. These two types of stromal cells may undergo myofibroblastic transformation by the transforming growth factor-β1 secreted by the proliferating biliary epithelial cells.

Prostatic signet-ring cell carcinoma: Case report and literature review

Signet‐ring cell carcinoma (SRCC) of the prostate is a very rare neoplasm and there have been only 38 cases reported to date. Here the 39th case of prostatic SRCC containing a small amount of neutral mucin, prostatic specific antigen (PSA) and prostatic specific acid phosphatase (PSAP) in the signet‐ring cells is reported. It was also found that some intracytoplasmic lumina were derived from the shallow or deep invagination of luminal membranes of cancer cells that formed the neoplastic glands. Using immunohistochemistry, a combination of monoclonal antibodies against cytokeratins 7 and 20 as well as PSA and PSAP may be useful in differentiating prostatic primary SRCC from metastatic SRCC originating in the gastrointestinal tract.

Expression of UDP-GalNAc : polypeptide N-acetylgalactosaminyltransferase isozymes T1 and T2 in human colorectal cancer

Abstract: Uridine diphosphate (UDP)-GalNAc: polypeptide N-acetylgalactosaminyltransferase (GalNAc transferase) catalyzes the initial step in mucin type O-glycosylation, and its expression has been assumed to be altered between normal epithelial cells and cancer cells. We studied the alteration of GalNAc transferase expression during the carcinogenesis of human colorectal epithelial cells. We produced polyclonal antibodies against synthetic polypeptides with specific sequence to two GalNAc transferase isozymes, T1 and T2. Surgically resected specimens from 50 patients with colorectal cancer were immunohistochemically stained, and the staining grade (percentage of positively stained cells) was compared between cancer and its normal counterpart in the same specimen. Significant signals for both T1 and T2 expression were seen in the supranuclear region of normal and cancer cells, indicating the subcellular localization of the enzymes in the Golgi apparatus. The prevalence of positive staining for T1 and T2 expression in colorectal cancer was significantly higher than that in normal epithelium (P < 0.05). However, the difference in staining grades between cancer and normal tissues varied in each patient. These results indicate that there is variability in the expression patterns of GalNAc transferase isozymes in normal and cancerous cells colorectal among individuals.

α Smooth muscle actin positive stromal cells in gastric carcinoma

Aims: To investigate the distribution and roles of α smooth muscle actin (ASMA) positive stromal cells (ASMA+ cells), which belong to the myofibroblast group, within gastric carcinomas, with reference to three histological types (diffuse type, intestinal type, and solid type). Methods: In total, 74 surgically resected gastric carcinomas (24 diffuse type, 43 intestinal type, and seven solid type) were examined. ASMA positive and high molecular weight caldesmon (HCD) negative stromal cells were regarded as ASMA+ cells. The distribution of CD34 positive stromal cells (CD34+ cells) was also analysed immunohistochemically. Results: In the 24 diffuse-type gastric carcinomas, six of the 13 carcinomas invading the subserosa had ASMA+ cells in the tumour stroma, whereas all six diffuse-type gastric carcinomas confined to the submucosa and all five invading the muscularis propria had no ASMA+ cells in the tumour stroma. In the 43 intestinal-type gastric carcinomas, only five of the 21 carcinomas confined to the submucosa had ASMA+ cells in the tumour stroma, whereas 21 of the 22 intestinal-type gastric carcinomas invading the muscularis propria and the subserosa had ASMA+ cell bundles in the tumour stroma. The distribution of CD34+ cells in diffuse-type and intestinal-type gastric carcinomas was similar to that seen in a previously published series. All seven solid-type gastric carcinomas examined had ASMA+ cells but not CD34+ cells in the tumour stroma. No stromal cells double positive for ASMA and CD34 were detected within the diffuse-type tumours examined. Conclusions: These results suggest that ASMA expression in stromal cells is associated with tumour stroma formation of diffuse-type gastric carcinomas invading the subserosa, intestinal-type gastric carcinomas invading the muscularis propria and subserosa, and solid-type gastric carcinomas.

Low-grade tubular-mucinous renal neoplasm with neuroendocrine differentiation: a histological, immunohistochemical and ultrastructural study.

Low‐grade tubular‐mucinous renal neoplasm (LGTMRN) was recently established as a distinct carcinoma classification. A 70‐year‐old, female traffic accident victim underwent a detailed examination that disclosed a huge mass in the lower pole of the left kidney. The patient underwent a nephrectomy based on a diagnosis of renal tumor. Macroscopically, the tumor was well demarcated and a whitish color with focal hemorrhage. Histological examination showed that tumor cells proliferated through tubular, trabecular, and solid growth patterns in the mucinous background. Focally, foci of clear cells or the proliferation of spindle cells was also observed. Nuclei were generally round and uniform in size. No abnormal mitotic figures were identified. Immunohistochemically, tumor cells were diffusely positive for AE1/AE3, vimentin and chromogranin A, and focally positive for cytokeratin (CK) 18, CK19, Ulex europaeus agglutinin‐1, epithelial membrane antigen, neuron‐specific enolase (NSE), CD9 and CD57. Ultrastructurally, tumor cells contained a moderate number of mitochondria, rough endoplasmic reticulum and dense‐core granules. No renin granules or glycogen were observed. Microvilli were focally seen. Our results render further evidence that LGTMRN is a distinct entity from the hitherto established renal neoplasms. Foci of clear cells and neuroendocrine differentiation should be added to the histological spectrum of LGTMRN.

Mesangial cell activation in the collagenofibrotic glomerulonephropathy

Abstract Collagenofibrotic glomerulonephropathy is a new disease entity of unknown pathogenesis, which is characterized by the deposition of type III collagen within the mesangial matrix. We have investigated a case in which many mesangial cells in the type III collagen-deposited glomeruli were α-smooth muscle actin (ASMA) positive and showed an increase of subplasmalemmal filaments, indicating the activation and myofibroblastic transformation. It is suggested that the activated mesangial cells may synthesize the type III collagen deposited in the subendothelial space and mesangial matrix.

Invasive micropapillary carcinoma of the urinary bladder : An immunohistochemical study of neoplastic and stromal cells

Abstract  A 66‐year‐old man complained of hematuria. A cystoscopy revealed a non‐papillary tumor and radical cystectomy was performed. Macroscopically, an ulcerative lesion was observed. Microscopically, the neoplasm showed a mixture of urothelial carcinoma, squamous cell carcinoma and micropapillary carcinoma. Immunohistochemically, micropapillary carcinoma cells were positive for cytokeratins 7 and 20, carcinoembryonic antigen and CA125. Additionally, myofibroblasts were distributed in a chicken‐wire pattern in the stroma of micropapillary carcinoma. Subsequently, the patient died of carcinoma 1 year after the onset of symptoms. Our results support the previous hypothesis that bladder micropapillary carcinoma runs an aggressive clinical course and suggest that micropapillary carcinoma may show the glandular differentiation of urothelial carcinoma and show the stromal reaction by myofibroblasts resembling that of carcinoma in other anatomic sites.

Anal canal neuroendocrine carcinoma with Pagetoid extension

A case of anal canal neuroendocrine carcinoma with Pagetoid intraepithelial extension is presented. An 80‐year‐old man was admitted to hospital with a complaint of pain in the anorectal region. Clinical examination revealed a hard and fixed mass in the anal canal, and subsequent biopsy of the lesion showed it to be a carcinoma. The surgically resected specimen showed a solid tumor measuring 3.4 × 3.2 cm within the area from the surgical anal canal to the anatomical anal canal. Tumor cells proliferated predominantly with compact nests. Many tumor cells had a high nuclear‐to‐cytoplasmic ratio, dispersed chromatin, and conspicuous nucleoli. Additionally, neoplastic cells focally formed a glandular structure. Some polygonal neoplastic cells were small with round nuclei. A rosette‐like arrangement was also focally observed. In addition, tumor cells exhibited Pagetoid extension into the overlying epithelium of the histological anal canal. Both the underlying original neoplastic cells and the Pagetoid spreading tumor cells showed cytoplasmic granules positive for Grimelius staining and immunopositivity for carcinoembryonic antigen, synaptophysin and cytokeratins 7 and 20. These findings are highly suggestive of neuroendocrine differentiation of adenocarcinoma cells. To the best of our knowledge, this is the first case of anal canal neuroendocrine carcinoma with Pagetoid extension into the overlying epithelium of the histological anal canal.