Expression of monocyte chemoattractant protein-1 and CC chemokine receptor 2 in non-small cell lung cancer and its significance.

Expression of monocyte chemoattractant protein-1 (MCP-1) and CC chemokine receptor 2 (CCR2) and its significance has been demonstrated in some cancer cells in recent clinical studies. However, the role of tumor MCP-1 and CCR2 expression in non-small cell lung cancer (NSCLC) remains unknown. The aim of the present study was to investigate the prognostic significance of MCP-1 and CCR2 expression in NSCLC cells. The relationship between MCP-1 and CCR2 expression in NSCLC cancer cells was examined by immunohistochemical staining of surgical specimens from 134 patients. Sixty-five of these patients had follow-up records. Kaplan-Meier analysis and Cox regression model were used to assess overall survival according to the presence or absence of MCP-1 and CCR2 expression in tumor cells. MCP-1 was detected in cancer cells of 107 NSCLC (79.9 %) and CCR2 was detected in cancer cells of 39 NSCLC (29.1 %). MCP-1 expression was correlated with sex, smoking habits, histology, and tumor size. Presence of MCP-1 in tumor cells was associated with better overall survival (P = 0.018). By multivariate analysis, MCP-1 expression in cancer cells showed an independent prognostic factor for overall survival (P = 0.002, hazard ratio [HR] = 0.256, 95 % confidence interval [CI] = 0.106-0.616). There was no significant relationship between CCR2 expression in tumor cells and clinical and pathological characteristics. Also, no significant positive correlation between MCP-1 and CCR2 expression was revealed by Spearman correlation analysis. Our data indicate that MCP-1 is overexpressed in NSCLC cells. Its expression in cancer cells is associated with better survival in NSCLC patients.

Relationship between programmed death-ligand 1 and clinicopathological characteristics in non-small cell lung cancer patients.

OBJECTIVE: To evaluate the correlation between programmed death-ligand 1 (PD-L1) expression in primary lung cancer cells, tumor associated macrophages (TAM) and patients' clinicopathological characteristics. METHODS: From 2008 to 2010, 208 non-small cell lung cancer patients who underwent surgery or CT-guided biopsy were recruited from Huadong Hospital, Fudan University. Immunohistochemistry staining was performed to evaluate the PD-L1 expression in both primary lung cancer cells and CD68 positive TAM. The relationship between PD-L1 expression and the clinical pathology was evaluated using χ(2) test. Spearman's rank correlations were used to determine the correlation between PD-L1 expression in tumor cells and macrophages. RESULTS: Positive PD-L1 expression in primary cancer cells was found in 136 (65.3%) patients, which were negatively correlated with lymph node metastasis (P=0.009) and smoking history (P=0.036). Besides, TAM with PD-L1 expression (found in 116 patients) was positively associated with smoking history (P=0.034), well-differentiation (P=0.029) and negative lymph node metastasis (P=0.0096). A correlation between PD-L1 expression in primary tumor cells and non-small cell lung cancer associated macrophages was found (r=0.228, P=0.021). CONCLUSION: PD-L1, secreted from TAM, might induce cancer cells apoptosis, and decrease lymph node metastasis.

[Cytogenetic profiles of follicular lymphoma].

OBJECTIVE: To study the cytogenetic profiles of follicular lymphoma (FL) in Chinese patients. METHODS: Conventional karyotype in 57 FL patients from Shanghai area was analyzed. Fluorescence in-situ hybridization (FISH) for t(14;18) and Bcl-6 and IgH gene rearrangement was performed in these cases. RESULTS: The most frequent breakpoints (frequency > or = 10% ) of the 57 FL cases were at band 14q32 (68.4%), 18q21 (38.6%), 3q27 (21.1%), 1q10 (15.8%) and 1q21 (12.3%). Nineteen (33.3%) of the 57 cases had t(14;18). The breakpoint of 18q21 and t(14;18) were more frequent in FL grade 1-2 and less frequent in FL grade 3 (57.6% vs. 12.5%; 54.5% vs. 4.2%, P < 0.05), whereas the 3q27/Bcl-6 rearrangement was more frequent in FL grade 3 and less frequent in FL grade 1-2 (37.5% vs. 9.1% , P < 0.05). The cohort of FL was more frequent in gains of chromosomes X, 1q, 5, 6p, 7 and 12q and losses of chromosomes 1p, 6p and 14q32. Gain of 18q was more frequent in FL grade 1-2 than in FL grade 3 (P < 0.05). Loss of 14q32 was more frequent in t(14;18) negative FL than in t(14;18) positive FL (P < 0.05). CONCLUSIONS: Compared with the data of Western patients reported in the literature, Chinese FL cases had distinct cytogenetic profiles from Western FL cases that the t(14;18) is less frequent and the gain of 1q is more frequent in Chinese FL cases, which are more significant in high grade FL.

Evaluating tumor-infiltrating lymphocytes in hepatocellular carcinoma using hematoxylin and eosin-stained tumor sections.

BACKGROUND: Tumor-infiltrating lymphocytes (TILs) constitute a prognostic factor in hepatocellular carcinoma (HCC). However, different methods of assessing TILs have various pre-analytical, analytical, and post-analytical challenges. The evaluation of TILs in hematoxylin and eosin (H&E)-stained tumor sections proposed by the International Immuno-Oncology Biomarker Working Group was demonstrated to be a reproducible, affordable and easily applied method in many tumors. AIM: To evaluate the prognostic significance of TILs in H&E-stained slides of HCCs. METHODS: This was a retrospective study performed in the hospital. HCC patients who underwent liver resection between 2015 and 2017 in Zhongshan Hospital were enrolled in this study. Patients who experienced recurrence or received therapy in addition to antiviral therapy before surgery at this time were excluded. A total of 204 patients were enrolled in the study. The ILs were counted manually in tumor sections stained with H&E under an optical microscope at 400 ×. The ILs were assessed separately in the center of the tumor (TILsCT), the invasive front (TILsIF), and peritumor (PILs) areas. Univariate and multivariate survival analyses were performed using a Cox regression model. P < 0.05 was considered statistically significant and all P-values were two-sided. RESULTS: Among the 204 patients, univariate analysis indicated that macrovascular invasion (MaVI) (P = 0.001), microvascular invasion (MVI) (P = 0.012), multiple tumors (P = 0.008), large tumors (> 10 cm) (P = 0.001), absence of a tumor capsule (P = 0.026), macrotrabecular histological subtype (P = 0.001), low density of TILsCT (P = 0.039), TILsIF (P = 0.014), and PILs (P = 0.010) were predictors of progression-free survival (PFS). Cox multivariate analysis indicated that MaVI (P = 0.009), absence of a tumor capsule (P = 0.031), low-density of TILsIF (P = 0.047) and PILs (P = 0.0495) were independent predictors of PFS. A three-category analysis was carried out by combining TILsCT, TILsIF, and PILs, after which HCCs were classified into immunehigh [(TILsCT)high, (TILsIF)high, and PILshigh, 83 cases], immunemod (tumors other than immunehigh and immunelow subtypes, 94 cases), and immunelow [(TILsCT)low, (TILsIF)low, and PILslow, 27 cases)] subtypes. The immunehigh subtype had a lower rate of MVI (40.96%) than the immunemod (61.70%, P = 0.017) and immunelow (66.67%, P = 0.020) subtypes. The recurrence rates of the immunehigh, immunemod and immunelow subtypes were 10.8%, 25.5% and 33.3%, respectively. CONCLUSION: HCC patients with high infiltrating lymphocytes tend to have a lower recurrence rate and less MVI. The evaluation of TILs in H&E-stained specimens could be a prognostic parameter for HCC.

[Urothelial hyperplastic lesion with endophytic growth pattern: a clinicopathologic study].

OBJECTIVE: To study the clinicopathologic features of urothelial hyperplastic lesion with an endophytic growth pattern and the role of immunohistochemistry and multitargeted fluorescence in situ hybridization (FISH) in the differential diagnosis. METHODS: Forty-one cases of urothelial lesions exhibiting endophytic growth patterns were reviewed and reclassified as inverted papilloma, urothelial carcinoma with an endophytic growth pattern, and florid von Brunn nest. The gains of chromosomes 3, 7, and 17 and loss of 9p21 was detected by FISH, and performed immunohistochemical staining for CK20, p53, and Ki-67. Follow-up data of 12 cases were obtained. RESULTS: (1) Twelve inverted papillomas sized 1.2 cm in average, consisted of anastomosing cords and nests with uniform width distribution involving the lamina propria, the central portion contained streaming cells with squamous metaplasia, and the periphery showed palisading. No or rare atypia and mitosis were found. Focal exophytic papillary component lined by less than 6 layers of normal urothelium were observed in 4 cases. (2) Twenty-four urothelial carcinomas with an endophytic growth pattern sized 2.1 cm in average, demonstrated the similar architecture with inverted papilloma, but exhibited thick columns and variable thickness of the cords, irregular size and shape of large nests with transition into solids. Mild to moderate cytologic atypia was shown, and mitotic figures ranged 1 to 8 per 10 HPFs. Exophytic papillary component was not observed in 3 cases, but the superficial urothelium showed dysplasia, while coexisted exophytic component in other cases was associated with low malignant potential or low grade tumor. (3) Five florid von Brunn nests sized 0.9 cm in average, had normal or hyperplastic urothelium, variable nests with cysts compacted in lamina propria, no cytologic atypia and mitosis. Twenty-one of 24 (79.1%) urothelial carcinomas with an endophytic growth pattern displayed abnormally positive results by multitargeted FISH, whereas all inverted papillomas and florid von Brunn nests were negative. Immunohistochemically, CK20 was weakly positive in 2 cases of urothelial carcinoma with an endophytic growth pattern, and negative in all inverted papillomas and florid von Brunn nests. p53 weakly stained 5% to 50% nuclei of the tumor cells in 16 cases of urothelial carcinomas with an endophytic growth pattern and 1 inverted papilloma. 1%-5% tumor cells expressed Ki-67 in urothelial carcinoma with an endophytic growth pattern, and less than 1% in inverted papilloma and florid von Brunn nests. Follow-up study revealed that 2 cases of urothelial carcinoma with an endophytic growth pattern had developed invasive carcinoma, underwent cystectomy, and metastasized remotely. No recurrence occurred in cases of inverted papilloma. CONCLUSIONS: Benign and malignant urothelial lesions with an endophytic growth pattern present histologic overlapping. Urothelial carcinoma with an endophytic growth pattern displays unique characteristics in morphology and immunohistochemistry. Multitargeted FISH analysis is helpful in the differential diagnosis.

[Value of spiral CT in diagnosis of cystic renal cell carcinoma].

OBJECTIVE: To investigate the image features and the diagnostic value of spiral CT for cystic renal cell carcinoma. METHODS: The clinical data and CT manifestations of 17 operated and pathologically proven cystic renal cell carcinoma were retrospectively analyzed. There were 12 males and 5 females with an average age of 47.3 years (33 - 82 years). Plain and contrast CT scan (Siemens somatom) single layer sensation 16 layer spiral CT had been performed before operation. The image of artery phase (30 - 40 s), venous (60 - 70 s) and excretory (120 - 180 s) were respectively obtained after contrast administration. Various image reconstructions were done using Siemens Wizard workstation based on the raw images. RESULTS: It was found that 5 cystic renal cell cancers located in the right kidney and 12 in the left kidney. The long dimension of the tumor arranged from 21 - 100 mm with an average of 57 mm. The tumor looked like a round or round-like shape with density similar to fluid on plain CT scan. Some cystic renal carcinomas had a thick wall. Some had single or multiple cystic spaces filled with fluid of different densities. Some had infiltrated out of kidney surface or into renal sinus. Some showed enhanced nodules on the wall. CONCLUSION: Cystic renal cell carcinoma has its own specific morphologic features in spiral CT scan. Spiral CT may be very helpful in the diagnosis of cystic renal cell carcinoma before operation.

Expression of the adipocytokine resistin and its association with the clinicopathological features and prognosis of pancreatic ductal adenocarcinoma.

Fat tissue is viewed as an active endocrine organ that secretes a variety of bioactive substances. Resistin, an adipocyte-secreted factor, is thought to be closely related to obesity, insulin resistance and inflammation, the three most significant risk factors for the progression of pancreatic cancer. However, the association between resistin and pancreatic cancer is still unknown. In this study, pancreatic tumor samples from 45 patients with pancreatic ductal adenocarcinoma were analyzed with immunohistochemistry for the expression of resistin. The correlation between resistin expression and clinicopathological features and prognosis were evaluated. Resistin staining was observed in 48.9% (22 of 45) of the cases. Resistin expression was more frequent in poorly differentiated tumors (9 of 9, 100%) compared to moderately differentiated tumors (11 of 28, 39.3%) and well-differentiated tumors (2 of 8, 25%) (p<0.01). The incidence of resistin expression in patients with Japan Pancreas Society stages III-IV (18 of 27, 66.7%) was significantly higher than in subjects with stages I-II (4 of 18, 22.2%) (p<0.01). Patients with resistin-stained tumors had significantly shorter relapse-free survival times (median, 9 months) than patients with negative tumors (median, 18 months) (p<0.05). In addition, multivariate analysis showed that resistin expression was an independent prognostic factor for relapse-free survival of patients with pancreatic ductal adenocarcinoma (p<0.05). These results demonstrate that resistin may influence the progression of pancreatic tumors and may be a useful predictor of relapse-free survival in patients with pancreatic ductal adenocarcinoma.