Survival Prediction Method Research Articles

Microdissection-based allelotyping discriminates de novo tumor from intrahepatic spread in hepatocellular carcinoma

A total of 103 cases of hepatocellular carcinoma (HCC) arising in native livers discovered at the time of transplantation underwent allelic loss analysis. HCC mutational allelotyping targeted 10 genomic loci (1p, 3p, 5q, 7q, 8q, 9p, 10q, 17p, 17q, 18q) using 18 polymorphic microsatellite markers situated in proximity to known tumor suppressor genes associated with human carcinogenesis. Gene analysis was performed on microdissected tissue samples removed from 4-μm thick histologic sections at specific topographic sites selected on the basis of representative cellular characteristics. Microdissection targets included largest tumor nodule at 2 locations as well as up to 3 additional tumor nodules in each case. HCC genotyping characteristics including mutational profile and cumulative fractional allelic loss (FAL) were correlated with clinical and pathologic features. Individual nodules of HCC showed 2 patterns of mutational change: (1) essentially concordant mutational profiles consistent with intrahepatic spread of tumor, or (2) discordant mutational profiles consistent with independent primary cancer formation. In 15 of 56 cases (27%) in which the HCC was in a multinodular, bilobar form (T4), sufficient discordance in the allelic loss profile enabled a more accurate T-stage classification with better prediction of recurrence-free survival. In conclusion, microdissection genotyping of HCC is an effective and objective means to (1) distinguish between de novo HCC tumor formation versus intrahepatic spread of cancer and to (2) improve on current methods for prediction of tumor aggressiveness and recurrence-free survival after liver transplantation. (H epatology 2003;37:871-879.)

Fuzzy neural network applied to gene expression profiling for predicting the prognosis of diffuse large B-cell lymphoma.

Diffuse large B‐cell lymphoma (DLBCL) is the largest category of aggressive lymphomas. Less than 50% of patients can be cured by combination chemotherapy. Microarray technologies have recently shown that the response to chemotherapy reflects the molecular heterogeneity in DLBCL. On the basis of published microarray data, we attempted to develop a long‐overdue method for the precise and simple prediction of survival of DLBCL patients. We developed a fuzzy neural network (FNN) model to analyze gene expression profiling data for DLBCL. From data on 5857 genes, this model identified four genes (CD10, AA807551, AA805611 and IRF‐4) that could be used to predict prognosis with 93% accuracy. FNNs are powerful tools for extracting significant biological markers affecting prognosis, and are applicable to various kinds of expression profiling data for any malignancy.

Usefulness of scintigraphy with technetium-99m galactosyl human serum albumin in prediction of prognosis of primary biliary cirrhosis

Prediction of survival of patients with primary biliary cirrhosis (PBC) has been based on results of blood tests and other indices of clinical condition, which may be affected by treatment. We earlier evaluated hepatic receptor imaging with 99mTc galactosyl human serum albumin as an alternative method for prediction of survival. To evaluate whether this method is useful for this purpose, we examined the cumulative survival rate of patients with PBC since their first examination by this method. The subjects were 60 patients with PBC, 10 healthy subjects, 65 patients with chronic hepatitis, and 196 patients with cirrhosis. Computer acquisition of gamma-camera data was started just before the injection of 99mTc galactosyl human serum albumin and was stopped 20 min later. As indices of hepatic functional reserve, the receptor index and the index of blood clearance were calculated. Among the patients with PBC, the receptor index was lower in those with stage IV than in those with stages I, II, or III, and the index of blood clearance was higher in patients with stage IV than in those with stages I, II, or III. On the basis of the receptor index, the patients with PBC were divided arbitrarily into two groups of roughly equal size: group A with a receptor index of ≥0.94, and group B with index <0.94. On the basis of the index of blood clearance, the patients were also divided into two groups of roughly equal size: group C with an index of blood clearance of <0.52, and group D with index ≥0.52. Cumulative survival rates were significantly lower in group B than in group A ( P=0.026), and lower in group D than in group C ( P=0.005). Regression analysis showed the index of blood clearance to be significantly related to survival. In conclusion, hepatic receptor imaging with 99mTc galactosyl human serum albumin can be used to noninvasively evaluate the hepatic functional reserve of patients with PBC and is useful clinically in establishing their prognosis.