Correlation of tissue transglutaminase expression on breast cancer tissue with time to relapse, overall survival, and clinical and molecular prognostic factors: a preliminary report.

PURPOSE: To correlate tissue transglutaminase (TTG) expression with the expression of molecules with prognostic significance in breast cancer patients and with classical clinical parameters (disease stage, histological grade, overall survival (OS), relapse rate, disease progression and time to treatment failure-TTF). PATIENTS AND METHODS: Paraffin-embedded tissue specimens from 68 breast cancer patients were studied retrospectively for TTG expression, estrogen (ER) and progesterone (PG) receptors, c-erbB-2, p53, Bcl-2, and Ki-67. Sixty-seven patients were females (mean age 60.5 years). Histology was ductal carcinoma in 53 (inflammatory in 2 and mucinous in 1 of them), lobular in 13 and tubular in 2 cases. Grade was 1 and 2 in 45 cases and 3 in 23. Forty-six patients had early-stage disease (I - IIB) and 22 advanced (IIIA - IV). RESULTS: Fifty patients had at least 1 favorable molecular prognostic factor while all but 3 had at least 1 unfavorable prognostic factor. Twenty-nine (42.6%) patients have relapsed so far (mean TTF 31.4 months). Fifty-two (76.5%) patients are still alive (mean OS 38.5 months). Of the 59 patients with nodal and/or metastatic disease 54 were expressing TTG and 32 Bcl-2. Five were not expressing either one while 22 were expressing both. Of the 9 patients without nodal and/or metastatic disease all but one were expressing TTG and Bcl-2. Analyzing these subgroups of patients there was sufficient evidence that TTG expression was correlated with a trend for prolonged survival both in patients with localized and extensive disease, while the coexpression with Bcl-2 was correlated with a trend for prolongation of TTF and OS, both in relapsing and nonrelapsing patients. However, these differences did not reach statistical significance. Similar comparisons of TTG expression with the presence of adverse prognostic factors verified a beneficial effect of TTG expression on OS in all subgroups. CONCLUSION: Our data suggest that TTG is an independent favorable prognostic factor for survival, possibly enhancing the apoptotic effect of chemotherapy.

Combined transarterial targeting locoregional immunotherapy-chemotherapy for patients with unresectable hepatocellular carcinoma: a new alternative for an old problem.

The prognosis for patients with advanced (stage III and IV) hepatocellular carcinoma (HCC) remains poor. Liver resection and liver transplantation have limited effects on overall survival. Our study was carried out to assess a novel therapeutic approach, which includes transarterial locoregional chemotherapy and in vivo locoregional dual immunostimulation, in patients with unresectable HCC. A group of 20 patients with stage III and IV hepatocellular carcinoma had 10 courses (once per day) of transarterial targeted locoregional immunotherapy with interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), emulsified in a Lipiodol-Urografin mixture. The target organs were the spleen and the liver tumor itself. One course of intrahepatic locoregional targeting transarterial chemotherapy was given 10 days after completion of immunotherapy (mitomycin C, carboplatin, Farmorubicin, Leucovorin, 5-fluorouracil, and IFN-gamma). This was followed after 2 months by another course of transarterial targeted locoregional immunotherapy-chemotherapy. All patients survived the operation and had a mean survival time of 18 months (4-22 months). There was a decrease in the tumor size of 14 of the 20 patients. Serum alpha-fetoprotein (AFP) levels declined in 14 patients, reaching normal levels in 12 patients. These preliminary results indicate that combined locoregional immunotherapy-chemotherapy is a promising therapeutic approach in patients suffering from advanced nonresectable HCC and merits further evaluation.

Combined immunopharmaceutical therapy of patients with unresectable pancreatic carcinoma.

BACKGROUND/AIMS: This paper presents the results of a prospective randomized study of targeting locoregional chemotherapy and targeting locoregional immunostimulation therapy implemented in 36, out of 66, patients with a histological diagnosis of pancreatic duct carcinoma seen by our group from 1991 to Sept. 1994. METHOD AND MATERIALS: Sixty-six patients with unresectable pancreatic duct carcinoma were separated into two groups. The first group received laparotomy (n = 30), with palliative gastric bypass (n = 8) or with palliative biliary bypass (n = 18). The second group received laparotomy (n = 36), with palliative gastric bypass (n = 9) or with palliative biliary bypass (n = 20), supplemented with locoregional immunostimulation and locoregional chemotherapy. This therapy consisted of ten days of infusion with Proleukin (IL2) and Imukin (gamma-IFN), emulsified in Lipidiol-Urographin. This infusion was performed five days trans-splenically and five days trans-tumorally. Fifteen days later, targeting locoregional chemotherapy was administered, again emulsified in Lipidiol-Urographin. RESULTS: All the patients in the first group are dead, with a mean survival of 4.5 months, as of November 1995. Presently, 47% (n = 17) of the second group have achieved a positive objective response, with a mean survival of 14.1 months. During re-exploration, eight patients became tumor free after pancreatic resection, which became feasible after our therapy and six are alive and have remained tumor free to date. CONCLUSION: Targeting locoregional immunotherapy, combined with locoregional chemotherapy appears to be a promising therapy, meriting further consideration for clinical application in patients with unresectable pancreatic ductal carcinoma.

Primary vascular bone sarcomas. A clinicopathological and immunohistochemical study of two cases.

Two cases of primary vascular bone sarcomas are reported. The first case presented a rather slow clinical course and a non-aggressive histological picture and was classified as hemangioendothelioma. The second was a frankly malignant tumor, already metastatic at the time of diagnosis, which was classified as angiosarcoma. Views concerning the nomenclature and the behavior of primary vascular bone sarcomas are also discussed.