Objective Gastroenteropancreatic neuroendocrine neoplasms （GEP-NENs） constitute a rare and heterogeneous group of tumors with varied biology and still constitute a diagnostic and therapeutic challenge for physicians...Objective Gastroenteropancreatic neuroendocrine neoplasms （GEP-NENs） constitute a rare and heterogeneous group of tumors with varied biology and still constitute a diagnostic and therapeutic challenge for physicians of all specialties. In the present study, we aimed to review and study the clinicopathological characteristics of GEP-NENs applying the World Health Organization （WHO） 2010 grading criterion. Methods A total of 48 patients were enrolled in the study. The study included patients diagnosed with GEP-NENs who were treated and followed up at our Hospital from January 2013 to December 2017. Data regarding clinicopathological features of the patients were retrospectively evaluated. The expression of neuroendocrine markers was measured using the immunohistochemical Ultra SensitiveTM S-P method of staining in 48 cases of primary GEP-NENs; and serum levels of neuron-specific enolase, carbohydrate an-tigen 19-9, and carcinoembryonic antigen in 36 GEP-NEN patients were measured using the electrochemiluminescence method. Results The median age at presentation was 59.3 （range 48-82） years, and 39 cases （81.3%） were seen between the 5th and 6th decades. There was a male predilection （male： female=3：1）. In 79.2% cases （38/48）, tumors were hormonally nonfunctional. The most common presentation was abdominal pain, and the most frequent primary site of the tumor was the rectum, followed by the stomach （n = 15, 31.3%）, colon （n = 5, 10.4%）, and so on. Of the 48 tumors, 16 （33.3%） were G1,6 （12.5%） cases were G2, 16 （33.3%） were neuroendocrine carcinoma （NEC）, and 10 （20.8%） were mixed adenoneuroendocrine carcinoma （MANEC）. According to the AJCC/UICC classification, 45.8% （n = 22） were diagnosed at low stage （stage Ⅰ or Ⅱ） while 54.2% （n = 26） were diagnosed at high stage （stage Ⅲ or Ⅳ） （the majority of NEC, G3, and MANEC）. A male preponderance was noted for all tumors except for G2 neoplasms, which showed no gender predilection. Thirty-nine patients underwent endoscopic biopsy. The lesions in 18.8% （n = 9） of the patients were indentified only radiologically. After the surgical procedures, 36 had at least one follow-up visit with a median follow-up duration of 5 months; the mean follow-up period was 28 ± 16 months. The one- year and three-year survival rates were 72.2% （26/36） and 61.1% （22/36）, respectively. This study did not find an effect of grade 3 （G3） of tumor on the short-term clinical outcome of these patients. In the survival analysis, NEN G3, higher stage （stage Ⅲ or Ⅳ） according to the AJCC/UICC classification （P 〈 0.05）, and metastases at diagnosis （P 〈 0.05） were associated with poorer prognosis. Conclusion Most GEP-NENs are nonfunctional and nonspecific in presentation. The most frequent primary site of the tumor was the rectum and the commonest ages at diagnosis were the 5th and 6th decades. Endoscopic biopsy is the main diagnostic and histological grading method for GEP-NEN. In the survival analysis, NEN G3, a higher stage according to the AJCC/UICC classification, and metastases at diagnosis are associated with poorer prognosis.展开更多
OBJECTIVE: To get insight on the regulatory mechanism of Ki-67 gene expression in malignant cell cycle. METHODS: Non-radioactive in situ hybridization (ISH) was undertaken, combined with immunohistochemistry to study ...OBJECTIVE: To get insight on the regulatory mechanism of Ki-67 gene expression in malignant cell cycle. METHODS: Non-radioactive in situ hybridization (ISH) was undertaken, combined with immunohistochemistry to study the Ki-67 gene transcription and translation in various human cells and tissues. HeLa cells and fresh colon cancer cells, tonsil, normal pancreas and pancreatic cancer tissues were used in this study. A 435 bp cDNA fragment located in exon 13 of the Ki-67 antigen gene was amplified by polymerase chain reaction (PCR). Digoxigenin-labelled antisense and sense RNA probes were prepared for detecting Ki-67 mRNA, combined with MIB-1 immunohistochemistry. RESULTS: Successful localization of Ki-67 mRNA in human HeLa cells, colon cancer cells, tissues specimen of the tonsil and pancreatic cancer tissue sections was accomplished by digoxigenin-labelling in situ hybridization technique. ISH to colon cancer cells and pancreatic cancer tissue slides showed that much stronger cytoplasm and perinuclear mRNA signals of the Ki-67 gene were present in malignant cells than in normal cells, which was in accordance with MIB-1 nuclear protein signals. CONCLUSIONS: A sensitive and practical in situ hybridization method for the analysis of Ki-67 antigen mRNA in human cell and tissue was developed. Abnormal transcription of exon 13 of Ki-67 gene might be responsible for malignant cell proliferation in colon and pancreatic cancer.展开更多
基金Supported by a grant from the Jining Medical University Teacher’s Research Support Fund(No.2018)
文摘Objective Gastroenteropancreatic neuroendocrine neoplasms （GEP-NENs） constitute a rare and heterogeneous group of tumors with varied biology and still constitute a diagnostic and therapeutic challenge for physicians of all specialties. In the present study, we aimed to review and study the clinicopathological characteristics of GEP-NENs applying the World Health Organization （WHO） 2010 grading criterion. Methods A total of 48 patients were enrolled in the study. The study included patients diagnosed with GEP-NENs who were treated and followed up at our Hospital from January 2013 to December 2017. Data regarding clinicopathological features of the patients were retrospectively evaluated. The expression of neuroendocrine markers was measured using the immunohistochemical Ultra SensitiveTM S-P method of staining in 48 cases of primary GEP-NENs; and serum levels of neuron-specific enolase, carbohydrate an-tigen 19-9, and carcinoembryonic antigen in 36 GEP-NEN patients were measured using the electrochemiluminescence method. Results The median age at presentation was 59.3 （range 48-82） years, and 39 cases （81.3%） were seen between the 5th and 6th decades. There was a male predilection （male： female=3：1）. In 79.2% cases （38/48）, tumors were hormonally nonfunctional. The most common presentation was abdominal pain, and the most frequent primary site of the tumor was the rectum, followed by the stomach （n = 15, 31.3%）, colon （n = 5, 10.4%）, and so on. Of the 48 tumors, 16 （33.3%） were G1,6 （12.5%） cases were G2, 16 （33.3%） were neuroendocrine carcinoma （NEC）, and 10 （20.8%） were mixed adenoneuroendocrine carcinoma （MANEC）. According to the AJCC/UICC classification, 45.8% （n = 22） were diagnosed at low stage （stage Ⅰ or Ⅱ） while 54.2% （n = 26） were diagnosed at high stage （stage Ⅲ or Ⅳ） （the majority of NEC, G3, and MANEC）. A male preponderance was noted for all tumors except for G2 neoplasms, which showed no gender predilection. Thirty-nine patients underwent endoscopic biopsy. The lesions in 18.8% （n = 9） of the patients were indentified only radiologically. After the surgical procedures, 36 had at least one follow-up visit with a median follow-up duration of 5 months; the mean follow-up period was 28 ± 16 months. The one- year and three-year survival rates were 72.2% （26/36） and 61.1% （22/36）, respectively. This study did not find an effect of grade 3 （G3） of tumor on the short-term clinical outcome of these patients. In the survival analysis, NEN G3, higher stage （stage Ⅲ or Ⅳ） according to the AJCC/UICC classification （P 〈 0.05）, and metastases at diagnosis （P 〈 0.05） were associated with poorer prognosis. Conclusion Most GEP-NENs are nonfunctional and nonspecific in presentation. The most frequent primary site of the tumor was the rectum and the commonest ages at diagnosis were the 5th and 6th decades. Endoscopic biopsy is the main diagnostic and histological grading method for GEP-NEN. In the survival analysis, NEN G3, a higher stage according to the AJCC/UICC classification, and metastases at diagnosis are associated with poorer prognosis.
基金boththeNationalNaturalScienceFoundationofChina (No 396 0 0 14 1)andtheNaturalScienceFoundationofZhejiangProvince (No 396 498
文摘OBJECTIVE: To get insight on the regulatory mechanism of Ki-67 gene expression in malignant cell cycle. METHODS: Non-radioactive in situ hybridization (ISH) was undertaken, combined with immunohistochemistry to study the Ki-67 gene transcription and translation in various human cells and tissues. HeLa cells and fresh colon cancer cells, tonsil, normal pancreas and pancreatic cancer tissues were used in this study. A 435 bp cDNA fragment located in exon 13 of the Ki-67 antigen gene was amplified by polymerase chain reaction (PCR). Digoxigenin-labelled antisense and sense RNA probes were prepared for detecting Ki-67 mRNA, combined with MIB-1 immunohistochemistry. RESULTS: Successful localization of Ki-67 mRNA in human HeLa cells, colon cancer cells, tissues specimen of the tonsil and pancreatic cancer tissue sections was accomplished by digoxigenin-labelling in situ hybridization technique. ISH to colon cancer cells and pancreatic cancer tissue slides showed that much stronger cytoplasm and perinuclear mRNA signals of the Ki-67 gene were present in malignant cells than in normal cells, which was in accordance with MIB-1 nuclear protein signals. CONCLUSIONS: A sensitive and practical in situ hybridization method for the analysis of Ki-67 antigen mRNA in human cell and tissue was developed. Abnormal transcription of exon 13 of Ki-67 gene might be responsible for malignant cell proliferation in colon and pancreatic cancer.
