Expert Consensus on Pathological Diagnosis of Intrahepatic Cholangiocarcinoma (2022 version).

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5th edition of the World Health Organization Classification of Tumours of the Digestive System.

Clinical characteristics, medical service utilization, and expenditure for colorectal cancer in China, 2005 to 2014: Overall design and results from a multicenter retrospective epidemiologic survey.

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer in China, however, publicly available, descriptive information on the clinical epidemiology of CRC is limited. METHODS: Patients diagnosed with primary CRC during 2005 through 2014 were sampled from 13 tertiary hospitals in 9 provinces across China. Data related to sociodemographic characteristics, the use of diagnostic technology, treatment adoption, and expenditure were extracted from individual medical records. RESULTS: In the full cohort of 8465 patients, the mean ± SD age at diagnosis was 59.3 ± 12.8 years, 57.2% were men, and 58.7% had rectal cancer. On average, 14.4% of patients were diagnosed with stage IV disease, and this proportion increased from 13.5% in 2005 to 20.5% in 2014 (P value for trend < .05). For diagnostic techniques, along with less use of x-rays (average, 81.6%; decreased from 90.0% to 65.7%), there were increases in the use of computed tomography (average, 70.4%; increased from 4.5% to 90.5%) and magnetic resonance imaging (average, 8.8%; increased from 0.1% to 20.4%) over the study period from 2005 to 2014. With regard to treatment, surgery alone was the most common (average, 50.1%), but its use decreased from 51.3% to 39.8% during 2005 through 2014; and the use of other treatments increased simultaneously, such as chemotherapy alone (average, 4.1%; increased from 4.1% to 11.9%). The average medical expenditure per patient was 66,291 Chinese Yuan (2014 value) and increased from 47,259 to 86,709 Chinese Yuan. CONCLUSIONS: The increasing proportion of late-stage diagnoses presents a challenge for CRC control in China. Changes in diagnostic and treatment options and increased expenditures are clearly illustrated in this study. Coupled with the recent introduction of screening initiatives, these data provide an understanding of changes over time and may form a benchmark for future related evaluations of CRC interventions in China.

Analysis of clinicopathologic features and gene mutations in gastrointestinal stromal tumor: a series of 58 patients.

BACKGROUND: In gastrointestinal stromal tumor (GIST), mutually exclusive gain-of-function mutations of c-kit and PDGFRα are associated with different mutation-dependent clinical features. We analyzed clinico-pathologic features and genotypes of GIST among patients in China. METHODS: Adult patients with GIST in the stomach, small intestine, colorectum, or extra-gastrointestinal areas were enrolled in this study. These patients had been subjected to surgical resection without imatinib (Gleevec) treatment at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2009 to January 2019. Samples were obtained for histopathologic examination. Mutations in c-kit and PDGFRα genes were analyzed by PCR and next generation sequencing (NGS). Clinico-pathologic characteristics of each gene were also analyzed. RESULTS: A total of 58 GIST patients was enrolled in this study. In terms of genotypes, there were 51 (87.9%) c-kit mutations, 5 (8.6%) PDGFRα mutations, and 2 (3.4%) wild-type mutations. In terms of cell types, there were 40 cases (69.0%) with spindle cell type, 3 cases (5.2%) with epithelioid cell type and 3 cases (5.2%) with mixed spindle-epithelioid cell type. Among the 4 mutant forms of c-kit exon-11, the most common were point mutations in 16 cases (38.1%), deletion mutations in 13 cases (31.0%), insertion mutations in 4 cases (9.5%), and mixed mutations in 9 cases (21.4%). Based on risk grade classification of the National Institutes of Health (NIH), 3 cases (5.2%) were very-low risk, 9 cases (15.5%) were low risk, 19 cases (32.8%) were medium risk, and 23 cases (39.7%) were high risk. Significant differences in cell type were identified across different gene types (P = 0.022). Similarly, differences in tumor risk were found among different mutant forms of c-kit gene exon-11 (P = 0.039). CONCLUSION: With c-kit mutations, spindle cell type prevalence exceeded that of the epithelioid cell type and mixed spindle-epithelioid cell type. Spindle and mixed spindle-epithelioid cell types were the most prevalent in the category of PDGFRα mutations. In wild type cases, spindle and epithelioid cell types were the most common. A high risk of deletion and mixed mutations, and intermediate risk of point and insertion mutations were observed in c-kit exon-11 mutation type.

CD56+ lymphoepithelioma-like carcinoma of the lung: A case report and literature review.

BACKGROUND: Lymphoepithelioma-like carcinoma (LELC) is a non-keratinizing carcinoma with rich lymphocytic infiltration, which primarily originates from the nasopharynx. Primary lung LELC is a type of lung cancer with a relatively low incidence. Herein, we report a rare case of lung LELC with expression of CD56. We also performed a literature review to summarize the epidemiological, clinical, and prognostic features of this disease. CASE SUMMARY: A 51-year-old man was admitted to Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College due to cough and chest pain lasting > 2 mo and 1 wk, respectively. Positron emission tomography-computed tomography and magnetic resonance imaging examinations revealed the presence of a mass in the right upper lobe with enlargement of lymph nodes and multiple bone metastases. According to the results of bronchoscopy and cervical lymph node biopsy, a diagnosis of lung LELC with CD56-positive staining (CD56+ lung LELC) was made. In the literature, 458 cases of lung LELC have been reported. However, only one other case of CD56+ lung LELC has been reported thus far. CONCLUSION: The mechanism and potential role of CD56 expression in CD56+ lung LELC require further investigation.

The Significant Influence of the Neuroendocrine Component on the Survival of Patients with Gastric Carcinoma Characterized by Coexisting Exocrine and Neuroendocrine Components.

BACKGROUND: Gastric adenocarcinoma patients with a neuroendocrine (NE) component are frequently observed in routine practice. Several previous studies have investigated the influence of a NE component on the survival of these patients; however, the results were inconsistent. METHODS: We retrospectively investigated a consecutive series of 95 gastric adenocarcinoma patients with a NE component and 190 gastric adenocarcinoma patients without a NE component. We adopted 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, and 90% as the cut-off proportions of the NE component, respectively, and analyzed the patients' overall survival according to the proportion of the NE component. RESULTS: The 1-, 3-, and 5-year actual survival rates of the patients with a NE component were 90.1%, 72.3%, and 67.2%, respectively, and for those without a NE component 94.2%, 79.3%, and 75.7%, respectively. The multivariate analysis showed that the patients with NE components >70% (HR: 2.156; 95% CI: 1.011, 4.597; p=0.047) and >90% (HR: 2.476; 95% CI: 1.088, 5.634; p=0.031) had significantly worse survival than those without a NE component. Only the diameter of tumors (>4.64 cm) (HR: 2.585; 95% CI: 1.112, 6.006; p=0.027) and pN3 (HR: 2.953; 95% CI: 1.051, 8.293; p=0.040) were independently associated with worse overall survival for gastric adenocarcinoma patients with a NE component (all p<0.05). CONCLUSION: Gastric adenocarcinoma patients with a NE component >70% and >90% have significantly worse survival than those without a NE component. Only the diameter of tumors and the number of metastatic lymph nodes are independent prognostic factors for gastric adenocarcinoma patients with a NE component.

The gene mutational discrepancies between primary and paired metastatic colorectal carcinoma detected by next-generation sequencing.

PURPOSE: To better understand the gene mutational status and heterogeneity between primary and metastatic CRC (mCRC) using a sensitive sequencing method. METHODS: The mutational status of EGFR, KRAS, NRAS, PIK3CA, ERBB2, BRAF, KIT, and PDGFRA was analyzed in 65 patients, with 147 samples of primary and paired live or lung metastatic CRC, using next-generation sequencing (NGS), quantitative RT-PCR (qPCR), and Sanger sequencing. RESULTS: Fifteen cases (15/22, 68.2%) of lung mCRC and thirteen cases (13/20, 65%) of liver mCRC harboured the same mutation profiles of KRAS, NRAS, or BRAF in the primary lesions. To all detected genes, 11 cases (11/22, 50%) of lung mCRC and 11 cases (11/20, 55%) of liver mCRC showed different mutational genes in the primary tumours. KRAS and BRAF mutations were more frequent in lung metastatic lesions (p = 0.004 and 0.003, respectively). The gene mutations in KRAS, NRAS, BRAF, and PIK3CA in the lung metastatic sites were more frequent than those in the liver metastatic sites (86.7 vs. 44%, respectively, p = 0.000). Some new mutations were not covered in the qPCR ranges but were detected by NGS. CONCLUSION: The study demonstrated that the discordance of gene mutational status between paired primary and metastatic tumours is rather high when detected by NGS. Evaluating the mutational status of both the primary and metastatic tumours should be considered in clinical mutation testing.

A nation-wide retrospective epidemiological study of gastroenteropancreatic neuroendocrine neoplasms in china.

BACKGROUND: Representative data on the gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) in Asian patients is rare, especially in China. This study aims to create a GEP-NENs profile of Chinese patients. METHODS: This was a hospital-based, nation-wide, and multi-center 10-year (2001-2010) retrospective study which collected GEP-NEN patients' information in tertiary referral hospitals. All 2010 inpatient GEP-NEN cases with confirmed pathology in the selected hospitals were included. The primary GEP-NEN sites were measured and the epidemiological and clinical information of each tumor site were compared. RESULTS: The most common primary sites for GEP-NEN were the pancreas (31.5%) and rectum (29.6%), followed by the cardia (11.6%) and body (15.4%) of stomach. Small intestinal and colonic NENs took up a relatively small proportion of all patients. Pancreatic and rectal NENs, rather than cardiac and gastric body NENs, tended to be found in younger (P<0.001), female (P<0.001), urban (P<0.001) residents with a higher education level (P=0.032) and were also diagnosed at earlier stage (P<0.001) and lower grade (P<0.001). Surgery remained the primary treatment method in all groups. CONCLUSIONS: More studies on the commonality and heterogeneity of GEP-NENs are warranted to improve diagnosis efficiencies and treatment outcomes.

Clinicopathological Characteristics and Prognosis of Colorectal Cancer in Chinese Adolescent Patients.

BACKGROUND: Colorectal adenocarcinoma rarely occurred in adolescent. Clinical feature and prognosis of this population are not clear until now. In addition, DNA mismatch repair (MMR) status may relate to the early disease occurrence. The present study aimed to perform a retrospective analysis of adolescent patients with colorectal cancer, including clinicopathological characteristics and prognosis. METHODS: The medical records of 11,503 patients diagnosed as colorectal cancer in Cancer Hospital, Chinese Academy of Medical Sciences from January 1999 to December 2009 were retrospectively reviewed. Finally, 19 patients who were between 10 and 20 years old were selected as the study group. We summarized the clinicopathological characteristics, analyzed the association with prognosis and assessed the expression of MMR protein by immunohistochemical method. RESULTS: The most common primary site was the right colon in 7 patients. Ten patients had Stage III colorectal cancer, 5 patients had Stage IV disease. Signet ring cell carcinoma was the most frequent pathological type (7/19). Deficient MMR was identified in 2 patients. The 5-year survival rate and median survival time were 23.2% and 26 months. Distant metastasis was identified as an independent prognostic factor (P = 0.02). CONCLUSIONS: Colorectal cancer in Chinese adolescents was very rare. The chinese adolecents with colorectal cancer were frequently diagnosed in the right colon, as Stage III/IV disease with signet ring cell carcinoma. The prognosis was relatively poor.

Identification of genomic alterations in pancreatic cancer using array-based comparative genomic hybridization.

BACKGROUND: Genomic aberration is a common feature of human cancers and also is one of the basic mechanisms that lead to overexpression of oncogenes and underexpression of tumor suppressor genes. Our study aims to identify frequent genomic changes in pancreatic cancer. MATERIALS AND METHODS: We used array comparative genomic hybridization (array CGH) to identify recurrent genomic alterations and validated the protein expression of selected genes by immunohistochemistry. RESULTS: Sixteen gains and thirty-two losses occurred in more than 30% and 60% of the tumors, respectively. High-level amplifications at 7q21.3-q22.1 and 19q13.2 and homozygous deletions at 1p33-p32.3, 1p22.1, 1q22, 3q27.2, 6p22.3, 6p21.31, 12q13.2, 17p13.2, 17q21.31 and 22q13.1 were identified. Especially, amplification of AKT2 was detected in two carcinomas and homozygous deletion of CDKN2C in other two cases. In 15 independent validation samples, we found that AKT2 (19q13.2) and MCM7 (7q22.1) were amplified in 6 and 9 cases, and CAMTA2 (17p13.2) and PFN1 (17p13.2) were homozygously deleted in 3 and 1 cases. AKT2 and MCM7 were overexpressed, and CAMTA2 and PFN1 were underexpressed in pancreatic cancer tissues than in morphologically normal operative margin tissues. Both GISTIC and Genomic Workbench software identified 22q13.1 containing APOBEC3A and APOBEC3B as the only homozygous deletion region. And the expression levels of APOBEC3A and APOBEC3B were significantly lower in tumor tissues than in morphologically normal operative margin tissues. Further validation showed that overexpression of PSCA was significantly associated with lymph node metastasis, and overexpression of HMGA2 was significantly associated with invasive depth of pancreatic cancer. CONCLUSION: These recurrent genomic changes may be useful for revealing the mechanism of pancreatic carcinogenesis and providing candidate biomarkers.

Genetic landscape of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

Malignant extra-gastrointestinal stromal tumor of the pancreas: report of two cases and review of the literature.

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that arise from the gastrointestinal tract. In rare cases, these tumors are found in intra-abdominal sites unrelated to the gastrointestinal tract, such as the mesentery, omentum and retroperitoneum. However, pancreatic extra-gastrointestinal stromal tumors are extremely rare, with only 14 previous cases reported. A 61-year-old man with no clinical symptoms had a routine check-up, during which an abdominal mass located in the pancreas tail was detected. Abdominal surgery was performed with resection of the pancreas tail and the spleen, and he was diagnosed with low-risk GISTs. Another 60-year-old man with no clinical symptoms underwent Computed tomography which revealed a well-demarcated tumor, 6 cm in diameter, in the head of the pancreas. He was diagnosed with pancreatic GISTs. Here, we describe two rare cases of pancreatic GISTs and review the cases previously reported in the literature.

Overexpression of Cdc25C predicts response to radiotherapy and survival in esophageal squamous cell carcinoma patients treated with radiotherapy followed by surgery.

Biomarker identification is crucial for the selection of patients who might benefit from radiotherapy. To explore potential markers for response and prognosis in patients with locally advanced esophageal carcinoma treated with radiotherapy followed by surgery, we evaluated the expression of cell cycle checkpoint-related proteins Chk2, Cdc25C, and Cyclin D1. A total of 56 patients with locally advanced esophageal squamous cell carcinoma were treated with radiotherapy followed by surgery. Pretreatment tumor biopsy specimens were analyzed for Chk2, Cdc25C, and Cyclin D1 expression by immunohistochemistry. High expression of Chk2, Cyclin D1, and Cdc25C was observed in 44 (78.6%), 15 (26.8%), and 27 (48.2%) patients, respectively. The median survival was 16 months (range, 3-154 months), with a 5-year overall survival rate of 19.6%. Overexpression of Chk2 was associated with smoking (P = 0.021), overexpression of Cdc25C was associated with patient age (P = 0.033) and tumor length (P = 0.001), and overexpression of Cdc25C was associated with pathologic complete response (P = 0.038). Univariate analysis demonstrated that overexpression of Cdc25C and pathologic complete response was associated with better survival. In multivariate analysis, Cdc25C was the most significant independent predictor of better survival (P = 0.014) for patients treated with radiotherapy followed by surgery. Overexpression of Cdc25C was significantly associated with pathologic complete response and better survival of patients with locally advanced esophageal cancer treated with radiotherapy followed by surgery. These results suggest that Cdc25C may be a biomarker of treatment response and good prognosis for esophageal carcinoma patients. Thus, immunohistochemical staining of Cdc25C in a pretreatment specimen may be a useful method of identifying optimal treatment for patients with esophageal carcinoma.

[Immunophenotypes and gene mutations in colorectal precancerous lesions and adenocarcinoma].

OBJECTIVE: To analyze immunophenotypes and gene mutations of colorectal precancerous lesions and adenocarcinoma, and to compare the difference of carcinogenetic mechanisms between the two precancerous lesions. METHODS: Fifty-three cases of colorectal serrated lesions including 30 hyperplastic polyps, 20 sessile serrated adenomas (SSA) and 3 mixed polyps were collected from January 2006 to June 2012.Forty-five cases of traditional adenomas and 50 cases of colorectal adenocarcinomas were also recruited. Thirty hyperplastic polyps, 20 cases of SSA, 3 mixed polyps and 45 traditional adenomas were investigated by immunohistochemistry for the expression of DNA mismatch repair (MMR) proteins (MLH1, MSH2 and MSH6) and DNA methyltransferase MGMT. Mutations of KRAS, BRAF and PIK3CA genes in 10 cases of SSAs, 10 traditional adenomas, 1 mixed polyps and 50 colorectal adenocarcinomas were analyzed by PCR followed by direct Sanger sequencing. RESULTS: (1) Only 3 cases of hyperplastic polyps lost MLH1 expression, and none of SSAs or traditional adenomas showed loss of MLH1. The negative expression rates of MSH2, MSH6 and MGMT in hyperplastic polyps and SSA were significantly higher than those of traditional adenomas. (2) KRAS mutation was found in 5/10 cases of SSAs, 5/10 traditional adenomas and 1/1 mixed polyps. (3) Colorectal adenocarcinomas harbored the mutations of KRAS (48%, 24/50), BRAF (6%, 3/50) and PIK3CA (4%, 2/50). CONCLUSIONS: Immunophenotypic and gene mutation profiles are different between colorectal serrated lesion and traditional adenoma. Alterations of MMR and MGMT expression play important roles in the pathogenesis of "serrated neoplasm". KRAS mutation is a significant genetic change in the early phase of colorectal carcinogenesis.

Clinicopathological and prognostic features of hepatoid adenocarcinoma of the stomach.

BACKGROUND: Hepatoid adenocarcinoma of the stomach (HAS) is a rare type of gastric carcinoma, which has its unique clinicopathological features and poorer prognosis than that of the ordinary gastric adenocarcinoma. At present, there is still a lack of understanding about this disease. The current study aimed to summarize and discuss the clinical, pathological, immunohistochemical, and prognostic features of this disease. METHODS: A total of 20 patients of HAS were retrospectively studied. All the patients were treated in Cancer Hospital of Chinese Academy of Medical Sciences between March 1998 and October 2009. Statistical analysis, including the Kaplan-Meier method, log-rank test and Cox model, were performed by the SPSS 15.0 software. RESULTS: Seventeen patients (85%) had at least 1 lymph node metastases; 17 patients (85%) received postoperative immunohistochemical examinations, with an alpha-fetoprotein (AFP) positive rate of 94.1% (16/17); 14 patients had distant metastases (including 12 liver metastases, 1 lung metastasis, and 1 celiac widespread metastases), and one simultaneously had anastomotic recurrence and liver metastases. The overall survival time was 2 - 99 months (median: 12.0 months). The 3-year survival rate of the 20 patients was 17.2%. The 3-year survival rate of patients with complete hepatocyte-like regions and those with both hepatocellular carcinoma and adenocarcinoma regions was 20.0% and 17.5%, respectively (P = 0.361). The survival difference among the radical surgery group, palliative surgery group and no surgery group was statistically significant (P = 0.022). The Kaplan-Meier method and log-rank test showed that surgery, pTNM stages, and adjuvant chemotherapy were associated with prognosis (P < 0.05). The Cox model only confirmed that the pTNM stages and adjuvant chemotherapy had statistical significance for the prognosis of HAS (P < 0.05) due to the limited cases. CONCLUSIONS: HAS is a special type of gastric carcinoma and has a poor prognosis. The pTNM stage is an independent risk factor for HAS. Multidisciplinary therapy, including surgery and chemotherapy, may improve the prognosis of HAS.

[The relationship between RACK1 expression and clinicopathologic information of esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the expression and relationship of receptor for activated C kinase 1 (RACK1) and clinical characteristics in esophageal squamous cell carcinoma (ESCC). METHODS: Western Blotting was conducted to detect the RACK1 expression in ESCC cell lines. Immunohistochemistry was performed to assay the expression of RACK1 and Ki67 in tumor tissues and adjacent normal epithelium from 113 ESCC patients in tissue microarray. The relationship between the RACK1 level and such clinicopathologic profiles as age, gender, location, smoking, differentiation degree and TNM (tumor, node, metastasis) stage were analyzed. RESULTS: The expression of RACK1 protein was significantly down-regulated in ESCC tissues as compared with the normal adjacent epithelium (χ(2) = 63.363, P < 0.01). An upregulated expression of RACK1 was observed in 72.5% (29/40) ESCC tissues of patients without a smoking history. And it was significantly higher than that in 46.6% (34/73) of patients with a smoking history (χ(2) = 7.040, P = 0.008). In addition, the rate of up-regulated of RACK1 was significantly higher in stage I and II group (63.8%, 44/69) than that in stage III group (43.2%, 19/44) (χ(2) = 4.616, P = 0.032). Moreover, the ESCC tissues with a higher Ki67 score showed a lower level of RACK1 than that with a lower Ki67 score (χ(2) = 8.261, P = 0.016). CONCLUSION: The expression of RACK1 is down-regulated in ESCC tissues and associated with smoking. The expression of RACK1 was associated with smoking, TNM staging and Ki67 score of ESCC.

[Correlation study of the overexpression of activated Cdc42-associated kinase 1 and the stage and prognosis of esophageal squamous cell carcinoma].

OBJECTIVE: To investigate the expression and relationship of activated Cdc42-associated kinase 1 (ACK1) and the clinical characteristics of esophageal squamous cell carcinoma (ESCC). METHODS: The ACK1 expression in ESCC cell lines was detected by Western blot. Immunohistochemistry was performed to assay the expression level of ACK1 protein in tumor tissues and adjacent normal epithelium from 105 ESCC patients in tissue microarray and 45 patients in normal tissue slices. Semi-quantitative RT-PCR(reverse transcription-polymerase chain reaction)was performed to determine the expression level of ACK1 mRNA in 45 pairs of ESCC frozen tissues. RESULTS: The expression level of ACK1 protein was significantly up-regulated in 48.6% ESCC tissues as compared with the normal adjacent epithelium in tissue microarray. The overexpression of ACK1 was significantly correlated with the lymph node metastasis and TNM stage of ESCC patients. The results of normal tissue slices were consistent with those of tissue microarray. Furthermore the overexpression of ACK1 was associated with a poor survival of ESCC patients (P = 0.030). The elevated mRNA level of ACK1 in ESCC tissues was correlated with the lymph node metastasis and TNM stage of ESCC patients. And a significant correlation was observed between protein and mRNA level of ACK1 (P = 0.021). CONCLUSION: The up-regulated expressions of ACK1 protein and mRNA are correlated with the progression and prognosis of ESCC.

microRNA-92a promotes lymph node metastasis of human esophageal squamous cell carcinoma via E-cadherin.

microRNAs (miRNAs) regulate gene expression at the post-transcriptional level and play important roles in tumor initiation and progression. Recently, we examined the global miRNA expression profile of esophageal squamous cell carcinoma (ESCC) and demonstrated that miR-92a was highly expressed in tumor tissues. In this study, we found that the up-regulation of miR-92a was significantly correlated with the status of lymph node metastasis and TNM stage in 107 ESCC patients. Moreover, the up-regulation of miR-92a was associated with poor survival of ESCC patients and might be used as an independent prognostic factor. Next, we investigated the role and mechanism of miR-92a in ESCC cells, and found that miR-92a modulated the migration and invasion but not apoptosis and proliferation of ESCC cells in vitro. We further demonstrated that miR-92a directly targeted the CDH1 3'-UTR and repressed the expression of CDH1, a tumor metastasis suppressor. In addition, restoring of miR-92a-resistant CDH1 expression in miR-92a-overexpression cells recovered the pro-metastasis activity of miR-92a. Taken together, we demonstrated that miR-92a promotes ESCC cell migration and invasion at least partially via suppression of CDH1 expression, and patients with up-regulated miR-92a are prone to lymph node metastasis and thus have poor prognosis.

[Small pancreatic cancer diagnosis and prognosis].

OBJECTIVE: To investigate the clinicopathological characteristics, diagnostic methods and prognosis of small pancreatic cancer. METHODS: From May 2000 to January 2007, 89 patients with pancreatic cancer underwent surgery in our hospital. Of those, 14 had a tumor < or = 2 cm in diameter (small tumor group), and the other 75 had a tumor >2 cm in diameter (controlled group). The clinicopathological data of all the cases were retrospectively reviewed and analyzed. RESULTS: In the small pancreatic cancer group, CT and MRI detected 66.7% (8/12) and 77.8% (7/9) of the tumors, respectively. Serosal infiltration was found in 2 cases, lymph node involvement in 3 cases, and retroperitoneal infiltration in 3 cases. The follow-up duration of this group was 4-86 months. The overall 3- and 5-year survival rates were 42.8% and 31.7%, while in the control group, the overall 3- and 5-year survival rates were 29.7% and 22.5%, respectively. The multivariate analysis showed that the lymph node involvement, serosal infiltration and retroperitoneal infiltration were independent risk factors (P<0.05). However, the tumor size was not shown to be an independent risk factor (OR value = 1.45, P = 0.971). CONCLUSION: CT and MRI are valuable in detecting small pancreatic cancer. Small pancreatic cancers are likely to have a better prognosis when compared with larger ones. Lymph node metastasis and local infiltration are independent predictors of prognosis but not tumor size.

Overexpression of Pin1 in non-small cell lung cancer (NSCLC) and its correlation with lymph node metastases.

BACKGROUND: Pin1 isomerizes the bonds of molecules important for numerous oncogenic and cell-signaling pathways, including Bcl-2, p53, c-Jun, beta-catenin, NF-kappaB, cyclin D1, c-Myc and Raf-1. This can cause a change in conformation leading to alterations in catalytic activity, protein-protein interactions, subcellular localization and protein stability. These alterations have been shown to be associated with cell transformation and cancer progression. Pin1 is overexpressed in several different human cancers. This is the first report of Pin1 overexpression in clinical samples of non-small cell lung cancer (NSCLC). METHODS: Protein expression levels of Pin1 in tumor and normal lung specimens were analyzed for expression of Pin1, cyclin D1, p53 and MDM2 using immunohistochemistry and compared to several clinicopathological characteristics. The mRNA expression of Pin1 was also analyzed using quantitative real-time RT-PCR and compared to clinicopathological characteristics. RESULTS: Pin1 protein was shown to be overexpressed in NSCLC tumor samples, and correlated with lymph node positive disease and tumor stage. High expression of MDM2 also correlated with lymph node positive disease and with poorly differentiated tumors. High expression of MDM2 also correlated with lymph node positive disease and with poorly differentiated tumors. High expression levels of Pin1 correlated with high levels of p53 or MDM2 protein, but did not show a correlation with cyclin D1. However, high levels of MDM2 correlated with cyclin D1 overexpression. Pin1 mRNA was expressed significantly more often in the tumors of smokers than of non-smokers. The relationship between the expression of protein and mRNA of Pin1 has obviously showed that protein expression isn't significantly associated with mRNA expression. CONCLUSIONS: Pin1 is overexpressed in many different cancers, including NSCLC, and may possibly be used as a tumor marker or as a target for cancer therapy.