Eui Keun Ham

Overexpression of cyclin D1 and cdk4 in tumorigenesis of sporadic hepatoblastomas

Abnormality of the cyclin D1/cdk4/p16INK4a/pRb pathway during tumorigenesis has recently been reported. Hepatoblastoma is a rare malignant liver tumor of childhood, but underlying abnormalities of cell-cycle regulating protein remain to be elucidated. The expression of cyclin D1, cdk4, p16 and retinoblastoma gene product (pRb) was studied by immunohistochemistry in 17 paraffin-embedded tissues consisting of both tumor and corresponding non-neoplastic tissues. Tumor tissues showed overexpression of cyclin D1 (13/17, 76%) and cdk4 (15/17, 88%). Eleven cases showed co-overexpression of both cyclin D1 and cdk4. No abnormal p16 or pRb expression was noted. In the group with a high score (+4) for cyclin D1 expression, a positive correlation with tumor recurrence was noted (P = 0.043). These data suggest that overexpressed cyclin D1 and cdk4 protein might play an important role in the tumorigenesis of hepatoblastoma and that in the group with high cyclin D1 expression, tumor recurrence may be more frequent.

IMMUNOHISTOCHEMICAL LOCALIZATION OF SURFACTANT APOPROTEINS IN USUAL INTERSTITIAL PNEUMONIA ASSOCIATED WITH PULMONARY CARCINOMA

Surfactant apoproteins A and B (SP‐A and SP‐B) are antigenic determinants of pulmonary surfactant complexes. The role and functional significance of these proteins are largely unknown and the pattern of expression is probably related to the functional maturation of type II pneumocytes. Differential expression of SP‐A and SP‐B was reported in the developing human lung but little is known of their expression in the chronic injury. We studied 5 surgical cases of usual interstitial pneumonia (UIP) associated with carcinoma to evaluate the expression of pulmonary surfactant apoproteins. These cases were immunohistochemically examined by the streptavidin‐biotin complex method using monoclonal antibodies HS‐1 and HS‐2 against pulmonary surfactant apoprotein A (SP‐A) and B (SP‐B), respectively. In UIP, SP‐B was expressed strongly in type II pneumocytes and Clara cells but bronchiolar epithelium and metaplastic squamous cell lines in the honeycomb lesion were non‐reactive. SP‐A showed a similar pattern but much weaker reactivity when compared to that of SP‐B. Type II pneumocytes in normal lung tissue exhibited weak immunoreactivity and no difference in the intensity of staining between SP‐A and SP‐B. Neither carcinomatous area nor metaplastic lining cells at honeycomb lesion show immunoreactivity to SP‐A and SP‐B. These results suggest that type II pneumocytes in the UIP are functionally immature in their expression of the apoprotein types and the metaplastic squamous cells or neoplastic transformed cells do not have molecular characteristics of type II pneumocytes. Microsc. Res. Tech. 42:234–238, 1998.