Hepatoid adenocarcinoma-Clinicopathological features and molecular characteristics.

Hepatoid adenocarcinoma (HAC) is a rare, malignant, extrahepatic tumor with histologic features similar to those of hepatocellular carcinoma. HAC is most often associated with elevated alpha-fetoprotein (AFP). HAC can occur in multiple organs, including the stomach, esophagus, colon, pancreas, lungs, and ovaries. HAC differs greatly from typical adenocarcinoma in terms of its biological aggression, poor prognosis, and clinicopathological characteristics. However, the mechanisms underlying its development and invasive metastasis remain unclear. The purpose of this review was to summarize the clinicopathological features, molecular traits, and molecular mechanisms driving the malignant phenotype of HAC, in order to support the clinical diagnosis and treatment of HAC.

[p53 mutations in sporadic colorectal cancers with microsatellite instability].

OBJECTIVE: To study p53 mutation and its association with microsatellite instability (MI)/replication error (RER) in sporadic colorectal cancer. METHODS: Fifty five cases of sporadic colorectal cancer were analyzed for MI/RER by PCR-based silver staining or ABI377 sequencer at following seven separate microsatellite loci: BAT-26, D2S119, D2S123, D3S1293, D8S282, D13S160 and D18S58. p53 mutations at exon 5 - 8 were detected by direct sequencing and its overexpressions performed by immunohistochemistry. RESULTS: p53 gene mutations were present in 38.2% (21/55) of the tumors and its overexpressions in 60% (33/55) with a concordance rate of 42%. MI or RER positive rate was 27.2% (15/55) or 14.5% (8/55). MI/RER + cancers showed a tendency of relatively high p53 total mutation and point mutation rates with 53.3% VS 32.5% and 53.3% VS 30% in MI group (P > 0.05) and with 62.5% VS 34% and 62.5% VS 30.2% (P > 0.05) in RER group respectively; but they had low protein expression rate with 46.7% VS 65% in MI group and 50% VS 62% in RER group (P > 0.05). There were no differences in p53 missense mutation rates and distributions at CpG sites with 40% VS 30% and 20% VS 12.5% (P > 0.05) between the two kinds of MI/RER tumors. Furthermore, each (CA)n microsatellite locus had no significant effect on p53 mutation. CONCLUSION: No significant relationship is found between MI/RER and p53 mutation/overexpression in sporadic colorectal cancer. But MI/RER tumor tends to have relatively high p53 mutation and low overexpression rates. In addition, there exist no differences in p53 missense mutation rates and distributions at CpG sites between the two kinds of MI/RER tumors.

Serum M2-pyruvate kinase: A promising non-invasive biomarker for colorectal cancer mass screening.

AIM: To explore the value of serum M2-pyruvate kinase (M2-PK) in colorectal cancer (CRC) mass screening. METHODS: We conducted a molecular epidemiology study in Hangzhou, China, from year 2006 to year 2008. Serum samples were collected from 93 CRC, 41 advanced adenomas, 137 adenomas, 47 non-adenomatous polyps, and 158 normal participants in a community setting. Serum M2-PK and carcinoembryonic antigen (CEA) were measured using Enzyme-linked immunosorbent assay. SPSS 16.0 software was used to perform data analysis. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificities were estimated for serum M2-PK in diagnosis of colorectal lesions and compared with CEA. RESULTS: Average serum M2-PK value among 158 normal people was 2.96 U/mL and not affected by gender (P = 0.47) or age (P = 0.59). Average serum M2-PK (U/mL) was 14.75 among stage III and 13.10 among stage I and II CRC patients, about 4 times higher than that among normal people. Average serum M2-PK was 8.58, 6.70, 5.13 and 2.51 U/mL among advanced adenoma, adenomas, non-adenomatous polyps, and inflammatory bowel disease patients, respectively. AUC for serum M2-PK was greater than that for CEA among all colorectal lesions. AUC for serum M2-PK was 0.89 (0.84, 0.94) (95% confidence interval), higher than that for CEA [0.70 (0.62-0.79)] in CRC stage I and II, 0.89 (0.84-0.94) vs 0.73 (0.63-0.83) in CRC stage III, 0.81 (0.74-0.86) vs 0.63 (0.53 - 0.73) in advanced adenomas, 0.69 (0.64-0.76) vs 0.54 (0.47-0.60) in adenomas, and 0.69 (0.62-0.78) vs 0.58 (0.48-0.68) in non-adenomatous polyps. The diagnostic sensitivity for all colorectal lesions increased with decrease in the cut-off value of serum M2-PK. The diagnostic sensitivity (%) of serum M2-PK was 100.00 for CRC, 95.12 advanced adenoma, 82.48 adenoma, and 82.98 non-adenomatous polyp. There were no CRC cases missed and 40.51% of unnecessary colonoscopies were avoided when the cut-off value was 2.00 U/mL. CONCLUSION: Serum M2-PK can be used as a primary screening test in CRC mass screening. It may be a promising non-invasive biomarker for CRC early detection.

[Significance of combined determination of CK19mRNA, carcinoembryanic antigen, neuron-specific enolase, and tissue polypeptide antigen in peripheral blood of patients with lung cancer].

BACKGROUND & OBJECTIVE: Cellular keratin, an indicator for cancer cell in circulation gains increasing attention. Although CK19mRNA as a gene marker used to identify micro-metastasis is of relatively high practical value, it lacks specificity and sensitivity in diagnosis of cancer. The aim of this study is to evaluate whether the combined detection of CK19mRNA with other tumor markers, such as carcinoembryanic antigen(CEA), neuron-specific Enolase(NSE), tissue polypeptide antigen(TPA), would improve the diagnosis of lung cancer. METHODS: The expression level of CK19mRNA in peripheral blood mononucleated cells (PBMCS) was determined by RT-PCR, The levels of CEA, NSE, and TPA in serum were determined by enzyme-linked immunosorbent assay (ELISA) and time-resolved fluorometry(TRF) in 91 patients with lung cancer, 33 with benign lung diseases (BLD) and 50 healthy controls. The data was analyzed by t test and chi 2 test. RESULTS: The positive rates of CK19mRNA, CEA, NSE, and TPA in lung cancer group (49.5%, 65.9%, 67.0%, and 83.5%, respectively) were remarkably higher than in BLD group(24.2%, 9.0%, 15.2%, and 9.0%, respectively) and in healthy control group (10.0%, 4.0%, 8.0%, and 6.0%, respectively) (P < 0.01). The positive rate of CK19mRNA was not statistically different in various histological subtypes (P > 0.05). Although the positive rate of CK19mRNA appeared to be associated with the clinical stage (stage I + II: 44.4%, stage III: 48.4%, stag IV: 54.2%), there was no statistical significance among the three groups (P > 0.05). The serum level (microgram/L)/positive rate of CEA(3.5/27.8%, 5.1/35.5%, and 8.5/58.3%, respectively), NSE (12.5/33.3%, 15.3/41.9%, and 24.7/58.3%, respectively), and TPA (1.1/44.4%, 1.8/58.1%, and 3.6/66.7%, respectively) in stage I + II, III, and IV appeared to be associated with the clinical stages of lung cancer, but no statistical significance among the three groups (P > 0.05). Combined detection of three or four tumor markers yielded significant higher effective accuracy in diagnosis of lung cancer than that of any of two tumor markers or single tumor marker (P < 0.05). In addition, the results showed that TPA, CEA, and NSE were relatively specific for squamous cell carcinoma (76.7%), adenocarcinomas (83.3%), and small-cell lung cancer (79.2%), respectively. CONCLUSION: The combined measurement of CK19mRNA with CEA, NSE, and TPA can increase diagnosis rate of lung cancer, can also provide potent diagnosis basis for treatment.