Naoe Tamaru

Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer

Although estrogen is known to play a crucial role in the pathogenesis of breast cancer, the molecular mechanisms underlying the action of estrogen remain elusive. In the present study, we focused on keratinocyte growth factor (KGF) and its receptor (KGFR) in the pathogenesis of breast cancer, as a growth factor mediating estrogen action, since significant roles of KGF were demonstrated in various steroid hormone-dependent tissues. First, using paraffin-embedded specimens from 42 breast cancer patients, we examined expression patterns of KGF and KGFR by both immunohistochemistry using newly generated antibodies and nonradioactive in situ hybridization with T–T dimerized synthetic oligonucleotide probes. We next compared the results with the expression of estrogen receptor (ER) α and β, proliferative activity and apoptotic frequency (TUNEL staining). Also, the similar approaches were taken to analyze the expression and role of KGF in ER-positive (MCF7, ZR-75-1) and ER-negative (SK-BR-3, MDA-MB-231) human breast cancer cell lines in vitro. In the surgical specimens, KGF was expressed in cancer cells as well as stromal cells in 19/42 cases (45%), while KGFR was found in cancer cells in 24/42 cases (57%). The distribution of protein and mRNA in the analysis of both KGF and KGFR expression generally coincided. Moreover, KGF expression was closely associated with the expression of ER α, and the coexpression of KGF and KGFR significantly correlated with lower TUNEL index, but not with proliferative activity. In accordance with the in vivo findings, KGF expression was detected only in ER α-positive MCF7 and ZR-75-1 cells in vitro. And more importantly, we found the inhibitory effect of KGF upon the induction of apoptosis by anticancer drugs in MCF7 cells. Collectively, our results indicate that ER α may be involved in KGF expression, and that KGF may play antiapoptotic roles, rather than mitogenic, in human breast cancer.

Intraductal papillary neoplasm of the bile duct extending superficially from the intrahepatic to extrahepatic bile duct

Intraductal papillary neoplasm of the bile duct (IPNB) or liver is a recently noted rare disease, and its pathogenesis remains unclear. Here we present a case of IPNB with an interesting morphology, which was treated by resection of the right hemiliver and extrahepatic bile duct. A 79-year-old woman was found to have a high alkaline phosphatase level and slight dilatation of the right intrahepatic bile duct on imaging studies. The right intrahepatic bile duct became dilated over a 2-year period; however, no solid mass could be detected, and tumor markers were not elevated. Hepatic resection was scheduled because a mucin-producing bile duct carcinoma of the liver was suspected. A right hemihepatectomy was conducted, and the extrahepatic bile duct was also resected after malignant cells were found in the surgical stump of the right bile duct and in the bile itself. Macroscopically, diffuse dilatation of the intrahepatic bile duct was noted, but no solid component or mucin within the duct was found. Histopathological findings revealed carcinoma in situ, IPNB, in the majority of intrahepatic bile ducts, with no lymph node metastasis, and it extended continuously to the epithelium of the common bile duct. No tumor recurrence or biliary dilatation was observed at follow-up 2 years after surgery. It is important to consider malignancy in the presence of a dilated bile duct and in the absence of any cause of occlusion. Complete resection of IPNB results in a good prognosis and no recurrence.

Better choice of fixatives provides better histological details of the alveolar-capillary interface

Aims: To evaluate lung disease, pulmonary tissues should be fixed by inflation. However, many histological sections prepared after inflation fixation show wire‐like alveolar septa with capillary collapse. We investigated the reason for this artefact. Methods: To evaluate the effect of fixatives, we used the following commercially available solutions: regular 10% neutral buffered formalin (NBF), 20% NBF, 10% and 5% formalin prepared by diluting the 20% NBF, modified formalin solution as a substitute for 10% NBF, and 10% formalin prepared by diluting the 100% formalin without any buffers. Results: The osmolarity of the fixative was found to be responsible for the collapse artefact. Ten per cent formalin, prepared by diluting 100% formalin, the commercially available substitute for 10% NBF, and 5% formalin prepared by diluting 20% NBF, yielded the best pulmonary tissue morphology, including that of the alveolar‐capillary interface. Conclusions: Pulmonary physicians and pulmonary pathologists should use a suitable fixative solution for obtaining a better pulmonary architecture as well as to preserve the tissue block in optimal condition for future assessment of pulmonary diseases.