Deletion at chromosome arms 6q16-22 and 10q22.3-23.1 associated with initiation of prostate cancer.

Loss of heterozygosity (LOH) at 6q16-22 and 10q22.3-23.1 is common chromosomal alteration in advanced prostate cancer and suggests that one or more tumor suppressor genes may lie within these chromosome arms. However, the genetic changes in early stage prostate cancer and premalignant lesions remain to be investigated. We used 11 informative microsatellite markers at 6q16-22 and 10q22.3-23.1 in Japanese patients to compare the frequency of LOH in 53 lesions of high-grade prostatic intraepithelial neoplasia (HGPIN), 38 cases (38 lesions) of incidental prostate cancer (IPC) and 107 cases (168 lesions) of clinical prostate cancer (CPC). The frequency of LOH at 6q16-22 with at least one marker was 38 and 49% in IPC and CPC cases, respectively. Similarly, allelic loss at 10q22.3-23.1 was present in 35 and 39% of IPC and CPC, respectively. High-frequency LOH was detected in both the clinically insignificant and significant prostate cancers at 6q16-22 and 10q22.3-23.1 (P>0.05). However, no allelic loss was detected in any markers at the same regions in HGPIN (0%), which is usually considered a premalignant lesion to prostate cancer. Deletions of both the chromosome regions, 6q16-22 and 10q22.3-23.1, are more likely important events in the initiation and/or promotion of prostate cancer.

Mutation analysis of the p51 gene and correlation between p53, p73, and p51 expressions in prostatic carcinoma.

BACKGROUND: p73 and p51 are genes possessing amino-acid similarities to p53. We previously found no mutation in p73 in prostatic carcinoma, but did find abnormal expression of the gene. Involvement of these genes in prostatic carcinogenesis is still poorly understood. METHODS: Mutation analysis of the p51 gene and allelotyping of 3q28, on which p51 lies, were performed. Expression of p53, p73, and p51 was examined using reverse transcription-polymerase chain reaction, and expression levels were compared. RESULTS: No mutation in p51 was found (0/55 cases). Loss of heterozygosity at 3q28 was detected in 6 of 28 cases (21.8%). By expression analysis we found that in p53, 4 of 38 cases (10.5%) showed downregulation. No cases showed upregulation of p53. In contrast, p73 and p51 were downregulated in 42.1 and 39.5% of cases, respectively, and upregulated in 31.5 and 34.2% of cases, respectively. Expression levels of p51 corresponded with those of p73 in 25 of 38 cases (65.8%). CONCLUSIONS: Somatic mutations in p73 and p51 are not important in prostatic carcinogenesis. These genes may be associated with tumors by expression levels and may have roles in addition to tumor suppression.

Three-dimensional observations of the human hepatic artery (Arterial system in the liver).

BACKGROUND/AIMS: We examined the three-dimensional structures of the hepatic artery. MATERIALS/METHODS: A 39-year-old man who died of brain hemorrhage was autopsied. The liver was perfused with physiological saline and 20% formalin from the hepatic artery and portal vein. More than 700 serial sections were obtained from a paraffin-embedded block, and vascular reconstruction was performed under a light microscope. RESULTS: The hepatic artery divides into the axial artery and the peribiliary branch given off from it. These two systems also connect to each other by a few anastomoses. The former systematically supplies arterial blood to all the parenchymal liver cells. The latter forms two layers of plexes around the bile duct. The inner capillary layer is afferent and the outer vascular layer is efferent to the bile duct. CONCLUSION: To maintain constant sinusoidal blood flow, the terminal portions of the axial arteries may contract and thereby divert blood to peribiliary branches through bifurcations and anastomoses. The blood flow of the peribiliary capillary plexus may affect bile flow. The hepatic artery may act as a functional mediator between portal flow and bile excretion.

Prognostic status of p53 gene mutation in canine mammary carcinoma.

BACKGROUND: The p53 gene mutations have been associated with the development of human breast and canine mammary neoplasms; breast carcinoma patients with alterations of p53 gene are considered to have a poor prognosis. Mammary carcinoma represents the most common malignant tumor in female dogs. However, the prognostic significance of p53 gene mutation in the dog has been unclear. STUDY DESIGN: The alteration in exons 5-8 of p53 gene in 69 canine mammary carcinomas were investigated by PCR-SSCP with direct sequence analysis and statistically analyzed to compare with other clinicopathological parameters including age, neuter, tumor size, stage, histology, p53 expression, recurrence and death from carcinoma. RESULTS: 12 out of 69 (17%) carcinomas showed p53 gene mutations. After a follow-up period of 30 months, multivariate regression analysis revealed that p53 gene mutation was only an independent risk factor for increased risk of the recurrence and death from mammary carcinoma. CONCLUSION: The p53 gene alterations might contribute to the prognostic status in canine mammary carcinomas, in a way comparable to that of human tumors.

[A patient with epilepsy, congenital alopecia and mental retardation: combination of atypical absence in waking and nocturnal partial seizure].

We report a 7-year-old girl with epilepsy, congenital alopecia, and mental retardation. She was hairless at birth. Very scanty hair, eyebrows and eyelashes appeared at 2 years of age. Developmental delay was first recognized at 6 years. Nocturnal partial seizures occurred at 4 years, and atypical absence in waking at 6 years. Electroencephalogram showed spike-waves in the centrotemporal area which increased and developed into a generalized continuous spike and wave complexes upon sleeping at the age of 7 years 1 month. Ictal electroencephalogram in atypical absence showed generalized 3 c/s spike and wave complexes. Skin biopsy of the scalp showed scanty, immature hair follicles and immature sebaceous glands. Whether this case is related to ectodermal dysplasia is unclear.

Autoimmune forms of chronic hepatitis associated with hepatitis C virus (HCV) infection with and without HCV-RNA: histological differences from pure autoimmune hepatitis and chronic hepatitis C.

Liver biopsy specimens of pure autoimmune hepatitis (pAIH), autoimmune forms of chronic hepatitis with positivity for anti-hepatitis C virus (anti-HCV) and negativity for HCV-RNA (cAIH-RNA(-)), autoimmune forms of chronic hepatitis with positivity for anti-HCV and HCV-RNA (cAIH-RNA(+)), and chronic hepatitis C (CHC) were compared histologically and statistically to clarify the histological character of the autoimmune form of chronic hepatitis with HCV infection. The following representative histological features were used to investigate: inflammation, fibrosis, plasma cell infiltration, lymphoid aggregates/follicles, non-suppurative destructive cholangitis, and the shape of the enlarged portal tracts. While a considerable overlap in histological features between the pAIH and cAIH-RNA(-) groups and between the CHC and cAIH-RNA(+) groups was recognized, the overlap between the pAIH and CHC groups was small. Significant differences were found between cAIH-RNA(-) and cAIH-RAN(+) groups, especially in necroinflammatory findings. In conclusion, most cases of cAIH-RNA(-) with histological features similar to those of pAIH were shown to be AIH. The remaining cases might be CHC with subsidence of viral duplication. Conversely, many cases of cAIH-RNA(+) with histological findings similar to those of CHC were shown to be CHC clinically mimicking pAIH. The remaining cases might represent coexistence of pAIH and HCV infection.

Evaluation of new monoclonal anti-MyoD1 and anti-myogenin antibodies for the diagnosis of rhabdomyosarcoma.

New monoclonal anti-MyoD1 and anti-myogenin antibodies were evaluated immunohistochemically to determine whether they are useful in discriminating rhabdomyosarcoma (RMS) from other soft tissue tumors in routinely processed sections. Neither MyoD1 nor myogenin was expressed in normal, mature striated muscle. In RMS, nuclear expression of MyoD1 and myogenin was found in 82 and 80% of non-overlapping cases, respectively. MyoD1 was generally expressed in small, primitive tumor cells, and larger cells exhibiting morphological evidence of skeletal muscle differentiation failed to express positive nuclear immunostaining. Positive nuclear staining for myogenin was stronger than that for MyoD1 in cases with abundant differentiated tumor cells, but was less prominent in cases in which small, primitive tumor cells predominated. No leiomyosarcomas, Ewing's sarcomas/peripheral primitive neuroectodermal tumors or other soft tissue tumors exhibited nuclear expression of MyoD1 or myogenin. In conclusion, both anti-MyoD1 and anti-myogenin antibodies are useful for diagnosing RMS and for discriminating RMS from other soft tissue tumors.

Papillary adenocarcinoma arising in placentoid bullous lesion of the lung: report of a case with immunohistochemical study.

We report the case of a 52-year-old man with papillary adenocarcinoma arising in placentoid bullous lesion of the lung, which is a rare cystic lung disease. Macroscopically, the cyst contained a soft villous tumor closely resembling the placental chorionic villi of early gestation. Histologic examination revealed the tumor to be papillary adenocarcinoma with an abundant stromal core, which comprised vascular and lymphatic vessels, lymphocytes, fat cells, and smooth muscle. Immunohistochemically, adenocarcinoma cells were positive for CAM 5.2, epithelial membrane antigen, and PE10 (antisurfactant apoprotein A antibody). These results indicate that the adenocarcinoma was derived from the component epithelial cells of the cyst. Based on the tumor's macroscopic and microscopic appearance and on the results of the immunohistochemical studies, we conclude that the cystic tumor in our case arose in a placentoid bullous lesion of the lung.

Enhanced CD34 expression of sinusoid-like vascular endothelial cells in hepatocellular carcinoma.

The immunohistochemical expression of CD34 (human hematopoietic stem cell and endothelial cell marker) and laminin were studied in chronic liver diseases and hepatocellular carcinoma (HCC) to elucidate whether their expression reflected phenotypic differences between non-cancerous sinusoids and sinusoid-like tumor vessels. In normal liver, hepatic sinusoids were always negative for CD34 and laminin. In chronic hepatitis and cirrhosis, the two antigens were sparsely expressed in capillarized sinusoids at periportal and perinodular area. In advanced HCC, CD34 was strongly and diffusely expressed by the endothelial lining of sinusoid-like tumor vessels. However, early-stage HCC showed a wide spectrum of CD34 expression from negative to focal and diffuse, strongly positive staining in sinusoid-like vessels. Laminin was strongly expressed in advanced HCC but not in early-stage HCC. The results indicate that the enhanced expression of CD34 by sinusoidal endothelial cells may reflect the phenotypic change of endothelial cells in chronic liver diseases and HCC, and that the expression may correlate with the processes of angiogenesis induced by hepatocarcinogenesis.

Immunohistochemical localization of ganglioside components in hepatocellular carcinoma and liver cirrhosis using monoclonal antibody.

BACKGROUND: In our previous studies (1, 2) a remarkable difference in the patterns of gangliosides was demonstrated between normal human liver and hepatocellular carcinoma (HCC) on thin layer chromatography, consisting of a marked increased in GM2 and the unidentified gangliosides. The proliferation of the unidentified gangliosides was also revealed in certain types of liver cirrhosis. The precise chemical structure of the unidentified components still remains to be elucidated, and there are no comprehensive data on these components investigated in liver tissue from patients with liver cirrhosis, HCC, or malignancies of the biliary and gastrointestinal tracts. In view of this, we studied the immunohistochemical localization of these ganglioside components in these tissues. EXPERIMENTAL DESIGN: Two unidentified gangliosides were extracted and monoclonal antibody were prepared. Localization of these gangliosides on tissue sections of liver obtained from HCC and liver cirrhosis, and malignancies of the biliary and gastrointestinal tracts was investigated by performing immunohistochemical staining using monoclonal antibody. The carbohydrate composition and sialic acid species of these components were determined by gas-liquid chromatography analysis. The sialic acid linkage to the terminal moiety of these components was also investigated by sialidase treatment. RESULTS: Staining with monoclonal antibody against specific gangliosides revealed dense brown granules in HCC tissue sections, whereas normal liver, kidney, and spleen sections were negative. Tissue sections of cirrhotic livers generally stained weakly except one case that showed slight to moderate staining. These antigens were immunohistochemically negligible in sections from one case each of gastric, colon, and common bile duct cancer. The ganglioside components identified in HCC were confirmed to be sialosylparagloboside with an alpha 2-6galactosyl terminus as determined by gas-liquid chromatography analysis and enzymatic hydrolysis with different sialidases. CONCLUSIONS: These components may be a useful marker in the detection of HCC and for subclassification of HCC from the standpoint of ganglioside metabolism.

[Non-traumatic retroperitoneal hemorrhage from renal adenoma].

A 37-year-old woman presented to our hospital with the chief complaints of stroke and sudden onset of pain in the left flank. An abdominal ultrasonogram showed a solid tumor and abdominal CT revealed a tumor 3 cm in diameter and a capsule with a heterogeneous interior at the left lower pole of the kidney. This tumor was accompanied by retroperitoneal hemorrhage. Selective left angiogram showed an avascular tumor with an artery entering the region surrounding the tumor itself. Based on the above mentioned findings, rupture of a renal angiomyolipoma was suspected. However, renal cancer could not be ruled out. Surgery was performed. At operation, a frozen section showed no malignancy, and partial nephrectomy was performed. The tumor measured 3.0 x 3.5 x 3.5 cm, and had a capsule that was 3 mm thick; its interior was filled with brown necrotic tissue mixed with red-brown coagulated blood. The histological diagnosis was a tubulo-papillary renal adenoma, but since the inside of the tumor had undergone extensive necrosis a well-differentiated adenocarcinoma could not be excluded. A renal adenoma manifesting clinical symptoms is rare, and this case of pain caused by retroperitoneal hemorrhage is the first to be reported in Japan. It is difficult to diagnose renal adenoma by preoperative imaging and intraoperative frozen section examination. Diagnosis is considered to be difficult in some cases even when examining permanent specimens. Therefore, the type of surgery used in affected patients should also be investigated in the future.

Ovarian and hepatic metastases of gastric carcinoma associated with high serum levels of human chorionic gonadotropin (hCG), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA): a case report.

A 45-year-old woman who underwent gastrectomy for gastric carcinoma which had metastasized to the liver and ovaries, showed high serum levels of hCG, AFP and CEA. To locate the source, an immunohistochemical technique was utilized. HCG-producing cells were detected in poorly differentiated adenocarcinoma of a primary tumor and an ovarian metastatic site, and AFP-producing cells in poorly differentiated adenocarcinoma forming a medullary pattern of primary site and metastatic foci. CEA-producing cells were found diffused in primary tumor and metastatic foci. From the viewpoint of oncodevelopmental gene expression (Cancer Res 36:3423, 1976), it is interesting that the serum levels of these three tumor markers (hCG, AFP, CEA) were elevated simultaneously.

Malignant mixed müllerian tumor of the ovary. Report of a case studied by immunohistochemistry.

A case of malignant mixed müllerian tumor of the ovary in a 57-year-old woman is reported along with the results of an immunohistochemical study. The tumor, measuring 16 x 10 x 9 cm, was composed predominantly of adenocarcinoma with a smaller amount of anaplastic carcinoma as an epithelial component and chondrosarcoma, liposarcoma, fibrosarcoma and rhabdomyoblasts as mesenchymal elements. Immunohistochemistry using paraffin sections demonstrated cytokeratin (CK) and epithelial membrane antigen (EMA), generally regarded as epithelial markers, not only in the epithelial component but also in chondrosarcoma cells. Vimentin and desmin, generally regarded as mesenchymal markers, were exhibited partly in carcinoma cells as well as in mesenchymal elements. Positive staining for S-100 protein was obtained not only in chondrosarcoma and liposarcoma cells, but also partly in adenocarcinoma cells. This intricate immunohistochemical picture reflected the histologic findings. It is noteworthy that both carcinoma cells and chondrosarcoma cells demonstrated simultaneous expression of CK, EMA, vimentin, desmin and S-100 protein. This somewhat unusual antigen expression by tumor cells may indicate a change in the nature of tumor cells due to microenvironmental factors.

[Intracranial invasion of neuroendocrine carcinoma: a case report].

A rare case of neuroendocrine carcinoma arising from the nasal cavity is reported. A 57-year-old female, who had been complaining of anosmia for 8 years, was admitted to the otolaryngological department because an intranasal tumor was found. Then, removal of the tumor and radiotherapy was carried out. After these procedures, the patient suffered from a high fever and CSF rhinorrhea. At this stage, our neurosurgical department was consulted. CT scan revealed a partially calcified low density mass with a slight enhancement effect at the left frontal base. Under the diagnosis of intracranial invasion by intranasal neuroendocrine carcinoma, the patient was operated on. Through bifrontal craniotomy and a combination of extra- and intradural approach, the tumor was excised. After that, the dura and the skull base were reconstructed. On histological examination, the tumor was found to consist of NSE positive cells forming some glandular structures. Electron microscopic study disclosed neurosecretory granules in the cytoplasmic process. These findings are typical of neuroendocrine carcinoma and compatible to those of the intranasal tumor previously removed. Neuroendocrine carcinoma is rare in itself and there have been reported only two cases of its invasion of the skull base. The clinical features, diagnostic procedures, pathological findings, and treatment of this tumor are discussed in this report.