c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and progression of intrahepatic cholangiocarcinoma.

AIMS: The c-erbB-2 and c-Met proto-oncogenes are important for tumour invasiveness and metastasis in many types of malignant tumours. Previous studies have indicated that these proteins are associated with carcinogenesis in intrahepatic cholangiocarcinoma. In this study, we examined c-erbB-2 and c-Met expression by immunohistochemistry in hepatolithiasis, intrahepatic cholangiocarcinoma and metastatic lymph node, in order to clarify whether these proteins play a role in carcinogenesis and tumour metastasis in intrahepatic cholangiocarcinoma. METHODS AND RESULTS: In hepatolithiasis, the staining for c-erbB-2 was positive in 14 of the 23 (61%) cases, while staining for c-Met was positive in eight of the 23 (35%) cases. In intrahepatic cholangiocarcinoma, staining for c-erbB-2 was positive in 45 of the 81 (55%) cases, while staining for c-Met was positive in 28 (35%) cases. The positivity of c-Met staining in intrahepatic cholangiocarcinoma was significantly higher in the differentiated type of cholangiocarcinoma than in the undifferentiated type. In addition, c-Met-positive staining had an inverted correlation with tumour size, the presence of perineural invasion and the presence of lymph node metastasis. c-Met staining had a significantly higher positivity in cases at an early stage of intrahepatic cholangiocarcinoma. In contrast, the positivity of c-erbB-2 staining in intrahepatic cholangiocarcinoma was significantly higher in cases with lymph node metastasis than in cases without. In metastatic lymph nodes, the staining for c-erbB-2 was positive in 20 of the 25 (80%) cases, while staining for c-Met was positive in six of the 25 (24%) cases. There was no difference in survival between c-erbB-2-positive and negative patients. However, the patients with c-Met-positive tumours had a significantly longer survival than those with c-Met-negative tumours in the medium survival term. The multivariate analysis showed the presence of lymph node metastasis, lymphatic permeation and histological differentiation to be independent prognostic factors. CONCLUSION: These results indicate that increased c-Met expression participates in cholangiocarcinogenesis and in the early developmental stages of intrahepatic cholangiocarcinoma, while increased c-erbB-2 expression contributes to the development of cholangiocarcinogenesis into an advanced stage associated with tumour metastasis.

Primary hepatic carcinoid tumor: case report and review of 53 cases.

BACKGROUND: Primary hepatic carcinoid tumor (PHCT) is a extremely rare. The authors describe a patient with PHCT and review previously published cases of the disease. CASE REPORT: A 75-year-old man, presenting with weight loss and pain in the right upper abdomen, had multiple masses in both lobes of the liver. He was diagnosed as PHCT by radiological examination, laboratory findings with high levels of 5-hydroxyindoleacetic acid (5-HIAA) in the serum and urine, and histological findings including positive staining of tumor cells for Grimelius and chromogranin A. The patient received totally transcatheter arterial chemoembolization (TACE) five times over 27 months; this treatment provided excellent palliation and caused a decrease in urinary 5-HIAA levels. Fifty-three cases of PHCT have been reported in the English-language literature. RESULTS: Analysis of these published cases revealed that PHCT occurs in the middle age (mean age = 48.2 years) and is more frequent in females (males/females = 20/33 cases). Of the symptomatic patients, the major findings is abdominal pain, fullness, and/or a palpable mass (56% of symptomatic patients). In contrast, only 2 cases out of 53 presented with symptoms of typical carcinoid syndrome. In most cases, PHCT was detected as a hypervascular lesion by radiological examination. By histological analysis, 80% and 84% of the cases were positive for Grimelius silver stain and immunohistochemically positive for chromogranin A, respectively. Surgical resection is the treatment primarily recommended with an 18% of recurrence rate and a 74% of a survival rate after 5 years. For unresectable and recurrent cases, TACE may be recommended.

Clinicopathologic features and postoperative prognosis of multicentric small hepatocellular carcinoma.

BACKGROUND: Assessment of clinicopathologic characteristics and postoperative prognoses for patients with multicentric hepatocellular carcinoma (HCC) is important to determine not only a need to operate, but also an appropriate treatment after hepatic resection. STUDY DESIGN: Between May 1990 and April 1998, among 116 patients with an initial hepatectomy for HCC measuring 3 cm or less in maximum diameter, 34 patients had multicentric HCC (MC group), and 82 patients had single nodular HCC (SN group). To clarify the clinicopathologic features of patients in the MC group versus the SN group, we compared both the clinicopathologic parameters and the postoperative prognosis after curative hepatectomy between the two groups. RESULTS: The percentages of patients positive for hepatitis B surface antigen and hepatitis C virus antibody were not significantly different between the two groups. No differences were noted in pathologic characteristics of the main tumor or tumor markers. On the other hand, in the MC group, the percentage of patients evaluated in a Child's classification as either B or C was significantly higher (p < 0.05) than that of patients in the SN group, indicating that patients with multicentric HCC have a poor hepatic functional reserve. Both survival and disease-free survival of patients in the MC group who underwent a curative hepatectomy did not differ statistically from those in the SN group. CONCLUSIONS: Our results indicate that hepatic resection is useful, even for patients with multicentric HCC, if a curative hepatectomy can be performed and liver function can be saved, despite their poor hepatic functional reserve.