Clinicopathological Characteristics and Prognosis of Colorectal Cancer in Chinese Adolescent Patients / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Immunophenotypes and gene mutations in colorectal precancerous lesions and adenocarcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>(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).</p><p><b>CONCLUSIONS</b>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.</p>

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

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.

Clinicopathological and prognostic features of hepatoid adenocarcinoma of the stomach / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>

Small pancreatic cancer diagnosis and prognosis / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics, diagnostic methods and prognosis of small pancreatic cancer.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>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.</p>

Analysis of prognostic and clinicopathologic factors in gastrointestinal stromal tumors of the stomach / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To identify the clinical pathological characteristics and prognostic factors in patients with gastrointestinal stromal tumors of the stomach.</p><p><b>METHODS</b>The data of 98 patients of gastric stromal tumors, leiomyomas, leiomyosarcomas, leiomyoblastomas, schwannomas and neurofibromas, collected from Mar. 1983 to Dec. 2001 in our hospital with complete clinical and pathological data, were investigated retrospectively. Gastric stromal tumors were diagnosed by reviewing the tumor slides stained with hematoxylin and eosin (H&E). Two histomorphologically representative areas of each tumor slides were identified and arrayed on a tissue microarray. Immunohistochemistry staining were performed using antibodies to c-kit (CD117), CD34, smooth muscle actin (SMA), Desmin and S-100 proteins. The relations of various clinicopathologic characteristics and outcomes were tested by univariate analysis and multivariate analysis.</p><p><b>RESULTS</b>Ninety-one patients were clearly identified as gastric stromal tumors from the 98 patients, who were diagnosed as gastric stromal tumor, leiomyoma, leiomyosarcoma, leiomyoblastoma schwannoma and neurofibroma (92.9%). The follow-up rate was 91% and the median follow up time was 54 months. The patient survival rates at 1, 5 and 10 years were 88.8%, 79.6% and 63.7% respectively. Univariate analysis showed that tumor size, mitotic count, tumor necrosis, nuclear pleomorphism, cell type, cell density, surgical procedure, mucosal invasion, age and lable index of Ki-67 were associated with prognosis (P<0.05). Multivariate analysis showed that tumor size, mitotic count, mucosal invasion and tumor necrosis were predictors of prognosis (P<0.05).</p><p><b>CONCLUSION</b>Tumor size of >10 cm, mitotic count of >10 mitoses per 50 high power fields, necrosis and mucosal invasion are often associated with an aggressive clinical course in gastric stromal tumors.</p>

Intra-abdomen extragastrointestinal stromal tumors: a clinicopathologic study on 30 cases / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathological characteristics and prognostic factors in patients with intra-abdomen extragastrointestinal stromal tumors (EGISTs).</p><p><b>METHODS</b>The data of 47 patients of mesenchymal neoplasms that arose from the abdominal cavity and retroperitoneum, collected from July 1987 to June 2003 in our hospital with complete clinical and pathological data, were investigated retrospectively. EGISTs were diagnosed by reviewing the tumor slides stained with hematoxylin and eosin (H&E). Immunohistochemistry staining were performed on CD117, CD34, smooth muscle actin, Desmin and S-100 proteins. The relations of various clinicopathologic characteristics and outcomes were examined.</p><p><b>RESULTS</b>Among the 47 cases, 30 tumors were confirmed to be EGISTs. Twelve cases arose from the mesentery, six from small omentum, eight from retroperitoneum and four from the abdominal cavity. The size of tumors ranged from 4 to 30 cm (median 12.5 cm) in diameter and the tumor cell components mainly included spindle cells (23 cases), epithelioid cells (4 cases), and mixed cells (3 cases). The follow-up rate was 90% and the median follow up time was 44 months. The patient survival rates at 1, 5 and 10 years were 79.7%, 59.5% and 45.4% respectively. Univariate analysis showed that tumor size >10 cm, tumor necrosis, mitoses > or =5/50HPF, obvious nuclear atypia, moderate and poor differentiated tumor cells were predictors of poor prognosis.</p><p><b>CONCLUSIONS</b>EGISTs have specific clinical behaviors. The parameters used for predicting GISTs prognosis are not completely applicable for EGISTs. Tumor necrosis, obvious nuclear atypia and mitoses > or =5/50HPF help to predict aggressive behaviors in EGISTs.</p>

Multivariate analysis of prognosis in gastrointestinal stromal tumor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To identify prognostic factors in patients with gastrointestinal stromal tumors (GIST).</p><p><b>METHODS</b>Hematoxylin and eosin (H&E) stained histopathological slides of tumors from patients with mesenchymal neoplasms growing in the gastrointestinal tract and abdomen were reviewed. Two histologically representative areas were identified and chosen for tissue microarray. Immunohistochemical staining was performed to demonstrate c-kit protein (CD117), CD34, smooth muscle actin, desmin and S-100 protein. The relations of various clinicopathologic features to outcome were analyzed.</p><p><b>RESULTS</b>The overall disease-specific survival of 194 patients was 93.5% at 1 year, 72.1% at 3 years and 63.2% at 5 years. Univariate analysis indicated that the tumor size, mitotic count, primary location, necrosis, high cellularity, mucosal invasion, mixed cell type, hemorrhage, direct tumor invasion of surrounding tissue, male sex, incompleteness of resection, cytologic atypia were significant predictors of survival. Multivariate analysis showed that tumor size, mitotic count, necrosis, direct tumor invasion of surrounding tissue and male sex were poor prognostic signs.</p><p><b>CONCLUSION</b>Tumor size and mitotic count are important prognostic factors. However, to evaluate the prognosis of these tumors, a surgical pathologist should incorporate multiple parameters into their histologic evaluation in attempt to reach an appropriate opinion on the aggressiveness of GIST.</p>

Analysis of prognostic factors in gastrointestinal stromal tumors of the small intestine / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the prognostic factors in patients with gastrointestinal stromal tumors of the small intestine.</p><p><b>METHODS</b>Tumor slides stained with hematoxylin and eosin from these patients were reviewed. Two histomorphologically representative areas were identified and arrayed on a tissue microarray. Immunohistochemistry staining were performed using antibodies to detect the expression of c-kit protein (CD117), CD34, smooth muscle actin, desmin, S-100, Ki-67, P53 and bcl-2 protein. The relationship between clinicopathologic features and prognosis was analyzed by univariate analysis.</p><p><b>RESULTS</b>The 1-, 3-, 5-year survival rate of 58 such patients were 98.3%, 69.7%, and 50.9% respectively. The prognosis was related with tumor size and gender by univariate analysis (P< 0.05).</p><p><b>CONCLUSION</b>More attention should be paid to the male patients with small intestine stromal tumors,especially those with tumors size> 5 cm, because those tumors are more likely to metastasize than smaller tumors (< or = 5 cm).</p>

Relationship between overexpression of the RIalpha subunit of the cAMP-dependent protein kinase and clinicopathological features of lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the relationship between the overexpression of PKA RIalpha mRNA and cliniopathological parameters in lung cancer.</p><p><b>METHODS</b>RT-PCR was used to detect the expression of PKA RIalpha mRNA in 54 cases with human lung cancer and matched normal tissues.</p><p><b>RESULTS</b>(1) The expression of PKA RIalpha mRNA was significantly higher in cancer tissue (66.7%) than in normal tissues (20.4%) (P < 0.01). (2) The expression was significantly correlated with TNM stage (P < 0.01), being increased with TNM stage. (3) The expression was significantly higher in patients with positive lymph nodes than in those with negative lymph nodes (P < 0.01). (4) There were no significant associations of PKA RIalpha mRNA expression with histological type, differentiation grade or size of the tumor.</p><p><b>CONCLUSION</b>This study indicates that the overexpression of PKA RIalpha mRNA may play an important role in the progression, metastasis and prognosis of lung cancer.</p>

Expression of different RASSF1 transcripts and its clinical significance in lung carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the expression of three different RASSF1 transcripts and its clinical significance in lung carcinomas.</p><p><b>METHODS</b>The mRNA expression of RASSF1A, RASSF1B and RASSF1C was detected by RT-PCR in 51 human lung cancer tissues and 51 matched normal tissues.</p><p><b>RESULTS</b>1. The mRNA expression of three RASSF1 transcripts was detectable in all non-cancer tissues. However, high rate of expression loss of RASSF1A and RASSF1B existed in lung cancer tissues, which was 53.2% (2851) and 37.3% (19/51), respectively. RASSF1C was expressed in all of the tumor tissues. 2. Loss or abnormal down-regulation of RASSF1A was positively related with lymph node metastasis and TNM stage (P < 0.05) and 3. RASSF1B and RASSF1C mRNA expression was not correlated with TNM stage, histological type, differentiation grade or smoking index.</p><p><b>CONCLUSION</b>There is a significant expression difference among the three RASSF1 transcripts in lung carcinoma. RASSF1A, closely associated with lymph metastasis and TNM stage of lung carcinoma, should be a new tumor suppressor gene.</p>