[Diagnostic value of ultrasound-guided core needle biopsy for soft tissue tumors].

OBJECTIVE: To study the diagnostic value and pitfalls of ultrasound-guided core needle biopsy (CNB) of soft tissue tumors. METHODS: One hundred and six cases of CNB specimens encountered during the period from 2007 to 2012 were enrolled into the study. The pathologic diagnosis using CNB was compared with that using surgical specimens. Diagnostic accuracy was analyzed using Chi-square test, with respect to the histologic pattern (such as spindle cell and myxoid), biologic behavior (benign versus malignant) and immunohistochemical results. The 59 cases of sarcoma were subdivided into three grades according to FNCLCC grading system. RESULTS: Histologic diagnosis could be made in 84.0% (89/106) cases. Thirteen cases were non-diagnostic on CNB. There were 4 cases on CNB showing diagnostic discrepancy with surgical specimens. Four cases of "benign lesions" on CNB found to be myxoid liposarcoma and lipoma-like liposarcoma upon resection. In general, myxoid pattern (9/17) seen on CNB showed less diagnostic correlation with surgical specimens, as compared to spindle cell and other histologic patterns (P < 0.01). The rate of diagnostic correlation was 79.7% (49/59) for the 59 cases of sarcoma studied, with grade 2 and grade 3 sarcoma showing better correlation (in contrast to 7/17 for grade 1 sarcoma) (P < 0.01). Comparative analysis showed no significant difference between benign/borderline tumors and sarcomas. The application of immunohistochemical study did not result in significant improvement in diagnostic accuracy on CNB. CONCLUSIONS: Ultrasound-guided CNB is a reliable tool in pathologic diagnosis of soft tissue tumors and shows a high accuracy rate especially for high-grade sarcoma. Tumors with myxoid pattern, lipomatous tumors and grade 1 sarcomas are associated with lower diagnostic accuracy on CNB. Correlation with clinicoradiologic findings would also be helpful in diagnostic evaluation and surgical planning.

[ICAM-1 469K/E gene polymorphisms increase the risk of gastric dysplasia].

OBJECTIVE: To investigate the influence of ICAM-1 469K/E gene polymorphisms on the risk of atrophic gastritis and dysplasia. METHODS: The ICAM-1 469K/E gene polymorphisms in a total of 372 subjects were detected by polymerase chain reaction-direct sequencing. All of the subjects were from Linqu County, a high risk area of gastric cancer in Shandong Province of northern China. All cases were initially diagnosed as normal or superficial gastritis at the beginning of this study. After a 5-year follow-up, the cases were subdivided into no progression group (no histological progression, n=137), progression group I (progressed to severe chronic atrophic gastritis, n=194) and progression group II (progressed to low-grade dysplasia, n=41). RESULTS: In all 372 subjects, the frequencies of KK, KE or EE genotype of ICAM-1 K469E were 50.5%, 39.2% and 10.2%, respectively. No significant differences were observed in the ICAM-1 469K/E genotype frequencies between the progression group I and no progression group (P>0.05). The frequencies of KK genotype (68.3%) were significantly higher in the progression group II than in the no progression group (49.6%, P=0.035), and also than in the progression group I (47.4%, P=0.015). An increased risk of the progressing to dysplasia from normal or superficial gastritis was found in the individuals with ICAM-1 469KK genotype [odds ratio (OR)=2.21, 95%CI, 1.10-4.42]. CONCLUSION: ICAM-1 469K/E gene polymorphisms are significantly associated with the risk of gastric low-grade dysplasia, but not related with severe chronic atrophic gastritis in a population with high risk of gastric cancer in Linqu County, Shandong Province, China.

Do young patients with colorectal cancer have a poorer prognosis than old patients?

BACKGROUND: Colorectal cancer (CRC) is generally a disease of the older population. The prognosis and clinicopathologic features of CRC in the young, compared with those in older patients, continue to be debated. The aim of this study was to compare the survival, clinicopathologic features, and tumor markers of CRC in patients aged 40 y or younger and older patients. METHODS: A total of 230 patients with CRC of stage I-III were assessed retrospectively, with an endpoint of recurrence or metastasis after curative operation. The markers CEA, MMP-2, and p27(kip1) were studied by immunohistochemistry in all patients. RESULTS: The young group comprised 28 (12.2%) patients aged 40 y or younger with a median age of 36 y. The remaining 202 patients (87.8%) comprised the old group, with a median age of 61 y. There were no statistical differences in gender distribution, tumor sites, tumor size, or gross type between the young and old groups. The young group had a higher incidence of mucinous adenocarcinoma (17.9%) than the old group (6.4%) (P = 0.035). The distribution of stage, differentiation grade, and extent of venous invasion were similar. The median disease-free survival time was 60 mo for the young group and 49 mo for the old. Univariate analysis revealed that this difference was not significant (P = 0.1158). Multivariate Cox regression analysis also demonstrated that the age of the patient was not an independent factor for the prognosis of CRC. There were no statistical differences between the young and old groups in the expression of CEA, MMP-2, or p27(kip1). CONCLUSIONS: The results of this study indicated that there was a subtle difference in the incidence of mucinous adenocarcinoma between young and old patients with CRC. However, stage I-III young patients had a similar disease-free survival period as the older patients. Other clinicopathologic characteristics, and tumor markers such as CEA, MMP-2, and p27(kip1), were also similar between young and old CRC patients.

[Hepatic epithelioid hemangioendothelioma in needle biopsy specimens: report of 5 cases with review of literature].

OBJECTIVE: To evaluate the pathologic diagnosis of hepatic epithelioid hemangioendothelioma (EH) in needle biopsy specimens. METHODS: Five cases of hepatic EH diagnosed in needle biopsies encountered during the period from 1999 to 2010 in Beijing Cancer Hospital were retrospectively reviewed. The specimens were formalin-fixed, paraffin-embedded and stained with hematoxylin and eosin. Immunohistochemical study was also carried out. RESULTS: All the 5 patients were females. The age ranged from 23 to 47 years (mean = 39 years). The tumors in 4 patients were multiple and diagnosed as "metastasis" on ultrasound examination. The blood test results in all of the 5 patients were normal. Histologically, the tumor cells had an epithelioid appearance and were arranged in cords, solid nests or isolation, amongst a myxoid or hyaline matrix. The tumor cells contained scattered intracytoplasmic vacuoles which sometimes harbored red blood cells. There was no evidence of significant cellular pleomorphism, high mitotic activity and necrosis. Immunohistochemically, all of the 5 cases were positive for at least two endothelial markers (CD31, CD34 and factor VIII-related antigen). Smooth muscle actin was expressed in 1 case. CONCLUSIONS: The diagnosis of hepatic EH can be established in needle biopsy specimens. The histologic pattern, when coupled with immunohistochemical findings, is useful in arriving at the correct diagnosis.

Phenotypic classification of gastric signet ring cell carcinoma and its relationship with clinicopathologic parameters and prognosis.

AIM: To distinguish subtypes of gastric signet ring cell (SRC) carcinoma by investigating the expression of gastric and intestinal phenotypic markers, and to study the significance of phenotypic classification in predicting tumor progression and outcome. METHODS: Immunohistochemistry was performed in 66 cases of SRC carcinoma with MUC2, VILLIN, CDX2, Li-cadherin antibodies as intestinal phenotype markers and MUC5AC, HGM, MUC6 antibodies as gastric phenotype markers, and the relationship was analyzed between the phenotypic expression pattern and clinicopathologic parameters, as well as the 3-year survival rate. RESULTS: Expression of intestinal phenotypic markers was positively associated with tumor size, wall invasion, vascular invasion, lymph node metastasis and tumor-node-metastasis (TNM) stage. Cases expressing one or more intestinal markers had a significant lower survival rate than cases expressing none of the intestinal markers. CONCLUSION: The SRC carcinomas expressing intestinal phenotype markers exhibited a high proliferative potential, bad biological behaviors and poor prognosis. Examination of phenotype expression may be useful in distinguishing histological type and in predicting the prognosis of gastric SRC carcinoma.

[The assessment of wall invasion of rectal carcinoma: correlation of endoluminal ultrasonographic and pathologic findings].

OBJECTIVE: To evaluate the accuracy of endoluminal ultrasonography (ELUS) in the preoperative assessment of wall invasion of rectal carcinoma and analyze its influencing factors. METHODS: ELUS was performed preoperatively in 117 patients with rectal carcinoma, in which no preoperative treatment was given. The results of ELUS were correlated with operative and pathologic findings according to the TNM classification. We observed the following factors and analyzed their impact on the accuracy of ELUS: tumor location, the depth of the tumor invasion, and the inflammatory cell infiltration and fibrosis peritumor. RESULTS: The overall accuracy of ELUS in T stage was 76.9% (90/117). The sensitivity of ELUS for pT(1), pT(2), pT(3) and pT(4) carcinoma was 87.5% (7/8), 51.7% (15/29), 85.7% (60/70), 80% (8/10), respectively. Misdiagnosis occurred in 27 cases, of which 14 cases were overstaged and 13 cases were understaged. The sensitivity for pT(2) carcinoma was the lowest; 14 cases were misdiagnosed, of them 13 cases were overstaged. Overstaging with ELUS for pT(2) carcinoma occurred mainly in these cases in which inflammatory cell infiltration, fibrosis or tumor involved more than one-third of muscularis propria. 13 cases were understaged, of which tumors in 7 cases were located in superior segment of rectum and 4 cases with obviously rectal stenosis. When tumor was located in middle or lower segment of rectum, misdiagnostic rate was 18.5% (17/92); while tumor was located in superior segment of rectum, misdiagnostic rate was 40% (10/25), and differences were statistically significant between two groups in misdiagnostic rate (P = 0.024). CONCLUSION: Although ELUS in the preoperative assessment of wall invasion of rectal carcinoma is useful, it is difficult to avoid overstaging and understaging of ELUS. The overstaging is an important unfavourable factor in assessing the invasion depth of pT(2) carcinoma with ELUS, and the depth of tumor invasion muscularis propria, and the depth of inflammatory cell infiltration and fibrosis might be responsible for overstaging. Obviously rectal stenosis and tumor being located in the superior segment of rectum might cause understaging.

[Abnormal expression of Thy-1 as a novel tumor marker in lung cancer and its prognostic significance].

OBJECTIVE: The purpose of this study was to investigate the expression of Thy-1 immunohistochemically in different lung tumors and its prognostic significance in non-small cell lung cancer (NSCLC) cases. We also evaluate relationship between Thy-1 and p53 expression status so as to find any clue about the mechanism. METHODS: In this study, we used anti-Thy-1/CD90 antibody to detect the expression pattern of Thy-1 in different lung tumor sections, which were embedded in paraffin blocks. The expressions of Thy-1 in 175 lung tissue cases, including different pathological types, were analyzed as tissue array form. We also detect expression status in 91 NSCLC among these cases and analyze the relationship between Thy-1 and p53. The relationship between Thy-1 expression and patients' survival was studied. RESULTS: We first found that anti-Thy-1 antibody can strongly stain a nuclear molecule in different type of lung cancer cells. Among lung cancer cases, 89 (56.7%) cases showed strong nuclear staining for Thy-1 specially. In univariate and multivariate analysis for 91 NSCLC patients we found TNM staging, lymph node status and Thy-1 overexpression in nuclei were independent factors to affect the prognosis of NSCLC patients. In lymph node non metastasis subgroup cases, Thy-1 negative patients had significant longer survival than Thy-1 positive cases (mean survival: 46.42 mons vs 38.56 mons, P = 0.0207). There was a significant association between Thy-1 and p53 expression (P < 0.0001). CONCLUSION: There is a significant overexpressed Thy-1 located in lung cancer cell nucleus as compared to the normal tissue or benign tumor cells of lung, and it is one of the factors effected on the prognosis of NSCLC patients. This finding suggests that Thy-1 maybe a novel latent malignant marker in the lung cancer pathology. The association between Thy-1 and p53 expression in nucleus suggests that p53 protein and Thy-1 may have some interaction.

Cancer/testis antigen expression and autologous humoral immunity to NY-ESO-1 in gastric cancer.

Gastric cancer has the highest mortality rate and the second-highest morbidity rate of all malignant tumors in China. Since cancer/testis (CT) antigens are expressed in various types of human tumors but generally not in normal tissue except for testis, they are promising antigens for cancer immunotherapy. NY-ESO-1, in particular, is the most immunogenic of the CT antigens. To study the feasibility of developing a CT antigen vaccine for gastric cancer, 101 gastric cancer samples were analyzed for the presence of NY-ESO-1 mRNA and that of 10 other CT antigen genes. Twelve out of 101 samples (11.9%) were found to be NY-ESO-1 mRNA-positive, 11 of them from advanced stage patients. In 7 of the 12 NY-ESO-1 mRNA-positive samples, the NY-ESO-1 protein was also detected by immunohistochemistry. An autologous humoral immune response to NY-ESO-1 was detected in 6 of 12 advanced stage NY-ESO-1 mRNA-positive patients, indicating that NY-ESO-1 is immunogenic in advanced stage gastric cancer. The serum from a patient with an NY-ESO-1 negative but LAGE-1 positive tumor was also found to be NY-ESO-1 antibody positive, possibly due to cross-reactivity between NY-ESO-1 and LAGE-1. All NY-ESO-1 mRNA-positive gastric cancer samples also expressed one to seven additional CT genes, revealing a tendency toward a clustered expression pattern, regardless of disease stage. About 74% of the samples expressed at least one CT antigen, most frequently MAGE-3 (41.6%). NY-ESO-1 and MAGE-3 are thus potential targets for a multivalent CT antigen vaccine.

Hepatic histopathology and postoperative outcome after preoperative chemotherapy for Chinese patients with colorectal liver metastases.

AIM: To assess the effects of preoperative treatment on the hepatic histology of non-tumoral liver and the postoperative outcome. METHODS: One hundred and six patients underwent hepatic resection for colorectal metastases between 1999 and 2009. The surgical specimens were reviewed with established criteria for diagnosis and grading of pathological hepatic injury. The impact of preoperative therapy on liver injury and postoperative outcome was analyzed. RESULTS: Fifty-three patients (50%) received surgery alone, whereas 42 patients (39.6%) received neoadjuvant chemotherapy and 11 (10.4%) patients received preoperative hepatic artery infusion (HAI). Chemotherapy included oxaliplatin-based regimens (31.1%) and irinotecan-based regimens (8.5%). On histopathological analysis, 16 patients (15.1%) had steatosis, 31 (29.2%) had sinusoidal dilation and 20 patients (18.9%) had steatohepatitis. Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone (42.4% vs 20.8%, P = 0.03); however, the perioperative complication rate was not significantly different between the oxaliplatin group and surgery group (27.3% vs 13.2%, P = 0.1). HAI was associated with more steatosis, sinusoidal dilation and steatohepatitis than the surgery group, with higher perioperative morbidity (36.4% vs 13.2%, P = 0.06) and mortality (9.1% vs 0% P = 0.02). CONCLUSION: Preoperative oxaliplatin was associated with sinusoidal dilation compared with surgery alone. However, the preoperative oxaliplatin had no significant impact on perioperative outcomes. HAI can cause pathological changes and tends to increase perioperative morbidity and mortality.

Polymorphisms of ICAM-1 are associated with gastric cancer risk and prognosis.

AIM: To investigate the association between single nucleotide polymorphisms (SNPs) in intercellular adhesion molecule-1 (ICAM-1) and the risk, biological behavior and prognosis of gastric cancer (GC) in Chinese population. METHODS: The study group consisted of 332 GC patients and 380 healthy controls. Genotyping was performed using polymerase chain reaction and the results were confirmed by sequencing. The association of ICAM-1 K469E polymorphisms and the risk of GC were studied, and the correlation of ICAM-1 K469E polymorphisms with the clinicopathological parameters and prognosis of the patients with complete clinical and follow-up data was analyzed. RESULTS: Carriers of AA genotype had a significantly increased risk of GC compared with carriers of AG and GG genotypes [odds ratios: 1.36; 95% confidence interval (CI): 1.01-1.84; P = 0.041]. GC patients with AA genotype were more prone to distant metastasis than those carrying AG and GG genotypes (18.9% vs 7.0%, respectively; P = 0.002). In addition, patients at stage IV had significantly more carriers of AA genotype than those of AG and GG genotype (27.4% vs 16.9%, respectively; P = 0.046). Follow-up study showed that the overall cumulative survival rate was 23.7% in AA genotype group and 42.9% in AG and GG genotypes group. In univariate analysis, AA genotype was correlated with the overall cumulative survival (P = 0.034). But in multivariate analysis, ICAM-1 polymorphism was not an independent prognostic factor for the overall survival (relative risk, 1.145; 95% CI: 0.851-1.540; P = 0.370). CONCLUSION: Polymorphisms of ICAM-1 K469E can be a useful biomarker for identifying individuals with higher risk of GC, predicting disease progression, and guiding individualized treatment.

Survival stratification panel of colorectal carcinoma with combined expression of carcinoembryonic antigen, matrix metalloproteinases-2, and p27 kip1.

PURPOSE: The prognosis varies greatly in colorectal carcinoma patients, even in the same stage. We examined the association between the expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27 kip1, and clinicopathologic features in patients with colorectal carcinoma to identify a possible panel of tumor markers in predicting prognosis of colorectal carcinoma. METHODS: The expressions of three individual markers in 127 colorectal carcinoma cases were analyzed by immunohistochemistry method. Univariate and multivariate analysis were performed to analyze the expression with the disease-free survival time in colorectal carcinoma. RESULTS: High expression of matrix metalloproteinases-2, carcinoembryonic antigen, and low expression of p27 kip1 were related to poor prognosis in univariate analysis (P = 0.0002; P < 0.0001; P = 0.0008). The expression of matrix metalloproteinases-2, carcinoembryonic antigen, p27 kip1, and tumor differentiation were independent prognostic factors for disease-free survival by Cox regression analysis. The coexpression panel of matrix metalloproteinases-2, carcinoembryonic antigen, and p27 kip had significant prognostic value in all patients (P AB = 0.0103; P(BC) = 0.0068; P CD = 0.0117). Multivariate analysis with Cox regression reveals that coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27 kip1 were independent prognostic factors as tumor differentiation in colorectal carcinoma. In different stages, coexpression tumor markers functioned in Stages II and III but not in the 19 cases of Stage I. The reason might be the number of patients was too small. CONCLUSIONS: The results of this study provided further evidence that the combination of tumor markers of matrix metalloproteinases-2, carcinoembryonic antigen, and p27 kip1 was more informative than any single tumor marker alone for the disease-free survival stratification of colorectal carcinoma. Coexpression of matrix metalloproteinases-2, carcinoembryonic antigen, and p27 kip1 might be a useful survival stratification panel for clinical management.

Ex-vivo analysis of CD8+ T cells infiltrating colorectal tumors identifies a major effector-memory subset with low perforin content.

Previous studies have indicated that the infiltration of CD8+ T cells in colorectal cancer is an independent predictor of increased survival but clinical observations have suggested that the cytotoxic function of CD8+ T cells infiltrating colorectal cancer may often be limited. In this study, we have assessed the phenotype of colorectal cancer CD8+ tumor-infiltrating lymphocytes (TILs) isolated ex vivo from tumor tissue, and assessed the perforin content of TIL with respect to their location using immunohistochemistry. We found that CD8+ T cells TILs isolated from colorectal cancer are mainly composed of antigen-experienced cells of effector memory type (TEM, CD45RA-CCR7-, and CD27+/CD28- or CD27-/CD28-), and contain only minor proportions of terminally differentiated CD8+ T cells (TEMRA, CD45RA+CCR7-). The perforin content of these TILs, however, is significantly lower than that of antigen-experienced T cells in PBMCs due to the much lower levels of perforin found in the CD27-CD28- subset in TILs compared with CD8+ T cells of similar phenotype in PBMCs.