Ken Saito

Vasculogenic mimicry and pseudo‐comedo formation in breast cancer

Tumors require a blood supply for growth and hematogenous metastases. Until recently, most research in this area has focused on the role of angiogenesis, the recruitment of new vessels into a tumor from preexisting vessels. Previously, in a study of breast cancer (IBC), in which we used established inflammatory breast cancer (IBC) xenografts (WIBC‐9) originating from a patient with IBC (Shirakawa et al., Cancer Res 2001:61:445–451), we reported observing vasculogenic mimicry (VM), a condition in which bloodstreams within cancer tissue are not accompanied by a lining of endothelial cells (ECs) (Shirakawa et al., Cancer Res 2002:62:560–566). In the present study, we examined 331 surgically resected breast cancer specimens for evidence of VM, using immunohistochemistry and laser‐captured microdissection (LCM) followed by nested reverse transcriptase polymerase chain reaction (RT‐PCR). Surprisingly, 7.9% (26 specimens) of the 331 specimens exhibited evidence of VM. Of these 26 VM specimens, 84.6% (22 specimens) exhibited pseudo‐comedo formation. RT‐PCR analysis of 8 microdissected typical VM specimens revealed expression of Tie‐2, Flt‐1, thrombin receptor and CD31 in 63, 50, 0 and 0% of specimens, respectively. In contrast, results of RT‐PCR analysis of 8 specimens from non‐VM tumors were negative for expression of these genes. The 26 VM cases tended to have a higher percentage of hematogenous recurrence (p = 0.059) and a lower percentage of 5‐year survival (p = 0.071) than the 305 non‐VM cases. However, there were no significant differences in tumor size, lymph node metastasis, estrogen receptors or progesterone receptors between the 2 groups (p > 0.1). Our results suggest that the existence of VM increases the likelihood of hematogenous metastases and is in inverse proportion to prognosis.

Ischemic Stroke and the Gene for Angiotensin-Converting Enzyme in Japanese Hypertensives

BACKGROUNDnThe ACE insertion/deletion (I/D) polymorphism is reported to be associated with myocardial infarction in both whites and Japanese. However, there have been no reports on the association of this polymorphism with stroke in each race. Furthermore, there are some racial differences in the demographics of cardiovascular disease. In Japanese, stroke (especially that which occurs in preexisting hypertension) is more common and coronary artery disease much less common than in whites. We propose that the ACE I/D polymorphism might be associated with hypertensive cerebrovascular disease in Japanese.nnnMETHODS AND RESULTSnTo study the association between the ACE I/D polymorphism and hypertensive cerebrovascular disease, we identified the ACE I/D genotype in 228 hypertensive and 104 normotensive Japanese subjects. Compared with its frequency (0.31) in the 90 hypertensives without lacunae detected by magnetic resonance imaging, the ACE*D allele frequency was significantly higher (0.47; P<.001) in the 138 hypertensives with silent or clinically overt ischemic stroke, whereas there was no significant difference between its frequency in hypertensives without lacunae and in 104 normotensive control subjects (0.34). The positive association between the ACE I/D genotype and ischemic stroke in hypertensive patients was independent of other risk factors.nnnCONCLUSIONSnWe found a positive association between the ACE*D allele and ischemic stroke in Japanese hypertensives in our study. The ACE*D allele may be an independent risk factor for the development of cerebrovascular disease in hypertensive patients.

Hypertensive Nephropathy and the Gene for Angiotensin-Converting Enzyme

To investigate the genetic determinants for microalbuminuria, we studied an insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene, which influences the plasma ACE level, in 333 consecutive hypertensive patients and 113 normotensive control subjects. The urinary albumin excretion rate was calculated by using a 12-hour urine collection (mean for two consecutive nights from 7 PM to 7 AM) in all 333 hypertensive patients. The ACE D allele frequency did not differ significantly between the hypertensive patients and the normotensive control subjects (0.37 and 0.33, respectively). Among the hypertensive patients, nephropathy (microalbuminuria and albuminuria) was more common (P < .001) in those with the ACE DD genotype than in those with other genotypes. The D allele frequency in the nephropathy group was significantly higher than that in the normoalbuminuric group (0.45 versus 0.32, chi 2 = 10.8, P < .001). These results indicate that ACE I/D polymorphism is a genetic determinant for hypertensive renal disease in hypertensive patients. This polymorphism might be a confounding factor involved in the association between hypertensive nephropathy and cardiovascular events.

EBER-1 expression in thymic carcinoma

The Epstein‐Barr virus‐encoded small nuclear RNA, EBER‐1, has been shown to be a suitable target for the in situ hybridization detection of EBV in routinely processed tissue specimens. We evaluated the presence of EBV in thymic carcinoma and invasive thymoma using EBER‐1 in situ hybridization on formalin‐fixed paraffin‐embedded tissue sections. EBER‐1 expression was demonstrated in a case of lymphoepithelioma‐like thymic carcinoma, but was not detectable in other thymic carcinomas including six squamous cell carcinomas, a clear cell carcinoma and seven invasive thymomas. As reported in three previous cases of EBV‐associated thymic carcinoma, lymphoepithelioma‐like thymic carcinoma was shown to be closely associated with EBV in our series.

Alpha-Fetoprotein-Producing carcinoma of the colon: Report of a case

We report herein the rare case of a 67-year-old man in whom alpha-feto-protein (AFP)-producing carcinoma originated in the transverse colon, describing the clinical course of the patient and the histological features of the tumor. At the age of 63, the patient had been diagnosed as having sigmoid colon carcinoma, and surgery was carried out. However, 4 years later, his fecal occult blood test was positive, and further investigation revealed a transverse colon carcinoma with liver metastasis. The serum AFP measured preoperatively was 10978 ng/ml. Resection of the transverse colon and a liver biopsy were performed, following which his serum AFP level decreased to 4804 ng/ml. Histology of the ulcerated lesion in the transverse colon showed a poorly differentiated adenocarcinoma with a medullary growth pattern. Using an immunohistochemical staining method, AFP-producing cells were detected in the transverse colon carcinoma and the liver metastasis. Based on our experience of this patient and a review of the literature on the few cases previously reported, we conclude that AFP-producing coloretal carcinoma has a tendency to produce blood-borne metastasis and to be associated with a poor prognosis.

p53 Mutation in carcinomas arising in ovarian cystic teratomas

Carcinomas arising in mature cystic teratomas of the ovaries from nine women were examined for the presence of p53 mutations. The nine tumors comprised six squamous cell carcinomas, one squamous cell carcinoma in situ, one undifferentiated small cell carcinoma, and one muco‐epidermoid carcinoma. Abnormal nuclear accumulation of the p53 protein was obsenred in four of the tumors. Genomic DNA was extracted from formalin‐fixed, paraffin‐embedded tissue blocks and subjected to polymerase chain reaction (PCR) for specific amplification of the p53 gene exons 5–8, followed by direct chemiluminescence sequencing analysis. A frameshift mutation in exon 8 (codon 278, CCT > del T; stop at codon 344) was detected in one poorly differentiated squamous cell carcinoma. The samples were also evaluated for the possible association of ‘benign’ and ‘malignant’ types of human papillomavirus (HPV) by PCR using universal primer sets. None of the samples contained detectable HPV genome. These data suggest that p53 mutations are relatively uncommon in secondary carcinomas developing in ovarian. dermoid cysts, although the number of samples studied was admittedly small.

Subcarinal neurogenic tumor: Report of a case

We present herein the rare case of a 63-year-old man in whom a subcarinal tumor, demonstrated by enhanced chest computed tomograms (CT), was subsequently confirmed to be a neurilemmoma by histological examination following tumor resection through a diagnostic thoracoscopy. Magnetic resonance imaging (MRI) and transesophageal ultrasonogram findings excluded the possibility of malignant lymphoadenopathy. As the patient was also found to have an elevated level of the squamous cell carcinoma (SCC) tumor marker which did not resolve postoperatively, close follow-up will be required.

A case of endometrial adenocarcinoma with microglandular hyperplasia-like pattern.

今回われわれは, 子宮内膜に発生したmicroglandular adenocarcinomaの1例を経験したので報告する.症例は65歳女性, 不正性器出血を主訴とし受診した.超音波検査にて内膜増殖症が疑われ内膜細胞診, 組織診が施行された.その細胞像は, 小型でやや大小不同を示す微小腺管構造が特徴的で, 粘液貯留により嚢胞状に拡張した腺管内には好中球がみられ, 一部で集籏し微小膿瘍状を呈した.腺管周囲の重積性の構成細胞は円形核, 細顆粒状のクロマチン, 明瞭な核小体をもち核問距離は不均等であった.細胞内粘液による核圧排像やシート状配列にみられた豊富な細胞質から, 高分化な粘液性腺癌と診断された.生検組織診でも, 頸部に発生するmicroglandular hyperplasiaに類似した組織像であったが, 内膜から得られた検体であること, 細胞異型がみられることから診断確定のため子宮内膜全面掻爬が行われた.その組織像もほとんど生検と同様であったが, 一部に類内膜腺癌の組織像が得られ, microglandular adenocarcinomaと診断, 子宮が摘出された.手術標本では, 腫瘍の大部分はrnicrogladularな構造を有する乳頭状増殖であったが, 深部の腫瘍は定型的な類内膜腺癌 (G1) で, 子宮筋層に浸潤していた.

A case of oxyphilic cell adenoma of the thyroid associated with intranuclear cytoplasmic inclusions and grooves.

We report a case of oxyphilic cell adenoma of the thyroid gland in a 79-year-old female. Fine needle aspiration cytology revealed isolated or sheetly-arranged tumor cells which had abundant eosinophilic granular cytoplasm. Eccentric nuclei showed intranuclear cytoplasmic inclusions and grooves. Histologically, a follicular adenoma, oxyphilic cell type was well-encapsulated and did not show vascular invasion or metastasis.

Significant factors influencing the accuracy of PTCD bile cytology for pancreatic cancers.

膵癌に対するPTCD胆汁細胞診の陽性率に関与する因子を知ることを目的に, 膵癌163例, 検査回数1010回の検討を行った. 特に手術的切除55例においては, 腫瘍の膵内胆管への浸潤度, 組織型などの諸因子と陽性率との相関の有無を検討した.1. 膵癌に対するPTCD胆汁細胞診の陽性率は52.8%であった.2. 検査回数が多いほど陽性率が高くなる傾向を示した.3. 偽陰性例の検査回数は陽性例に比べ少なかった.4. 担癌患者において1回の検査で陽性となる確率は21.8%であった.5. 膵内胆管に露出しない膵癌の細胞診は陰性で, 膵内胆管への浸潤度が高いほど陽性率が高くなる傾向を示した.6. 血清ビリルビン値も閉塞の強さに相関する傾向を示し, 膵癌が胆管に露出しなくとも黄疸をきたす症例が含まれた.7. 組織型では, 高分化型管状腺癌に比べ中分化型管状腺癌の陽性率が高かった.8. 腫瘍の大きさ, 間質の量と陽性率には相関がみられなかった.