Strong prognostic value of nodal and bone marrow micro-involvement in patients with pancreatic ductal carcinoma receiving no adjuvant chemotherapy

AIM： To study the prognostic value of adjuvant chemotherapy in patients with pancreatic, ductal adenocarcinoma. METHODS： Lymph nodes from 106 patients with resectable pancreatic ductal adenocarcinoma were systematically sampled. A total of 318 lymph nodes classified histopathologically as tumor-free were examined using sensitive immunohistochemical assays. Forty-three （41%） of the 106 patients were staged as pT1/2, 63 （59%） as pT3/4, 51 （48%） as pNo, and 55 （52%） as pN1. The study population included 59 （56%） patients exhibiting G1/2, and 47 （44%） patients with G3 tumors. Patients received no adjuvant chemoor radiation therapy and were followed up for a median of 12 （range： 3.5 to 139） mo.RESULTS： Immunostaining with Ber-EP4 revealed nodal microinvolvement in lymph nodes classified as ＂tumor free＂ by conventional histopathology in 73 （69%） out of the 106 patients. Twenty-nine （57%） of 51 patients staged histopathologically as pNo had nodal microinvolvement. The five-year survival probability for pN0-patients was 54% for those without nodal microinvolvement and 0% for those with nodal microinvolvement. Cox-regression modeling revealed the independent prognostic effect of nodal microinvolvement on recurrence-free （relative risk 2.92, P = 0.005） and overall （relative risk 2.49, P = 0.009） survival. CONCLUSION： The study reveals strong and independent prognostic significance of nodal microinvolvement in patients with pancreatic ductal adenocarcinoma who have received no adjuvant therapy. The addition of immunohistochemical findings to histopathology reports stratification of patients with may help to improve risk pancreatic cancer.

L1 is a potential marker for poorly-differentiated pancreatic neuroendocrine carcinoma

AIM： To determine the expression of L1 in pancreatic neuroendocrine tumor and to correlate it with WHO classification of this tumor. METHODS： We retrospectively analyzed L1 expression in 63 cases of pancreatic neuroendocrine tumor by immunohistochemistry on paraffin sections of primary tumors or metastases. Staining was performed by peroxidase technique with monoclonal antibody U3127.11 against human L1. All tumors were classified according to WHO classification as well-differentiated neuroendo- crine tumors and carcinomas or poorly-differentiated neuroendocrine carcinomas. RESULTS： LI was detected in 5 （7.9%） of 63 pancreatic neuroendocrine tumors. Four （44.4%） of 9 poorlydifferentiated carcinomas expressed L1. In contrast, only 1 （1.9%） of 54 well-differentiated tumors or carcinomas was positive for LI. No expression was found in Langerhans islet cells of normal pancreatic tissue. Cross table analysis showed a significant association between L1 expression and classification of neuroendocrine tumors of the pancreas （P〈0.01）. CONCLUSION： L1 is specifically expressed in poorlydifferentiated pancreatic neuroendocrine carcinomas that are known to have the worst prognosis. L1 might be a marker for risk prediction of patients diagnosed with pancreatic neuroendocrine carcinomas.

Association of rare SPINK1 gene mutation with another base substitution in chronic pancreatitis patients

AIM: To verify and expand the known spectrum of serine protease inhibitor Kazal type 1 (SPINK1) gene mutations in chronic pancreatitis. METHODS: DNA extracted from 172 chronic pancreatitis patients was assayed for SPINK1 gene mutations by PCR and DNA sequencing. A control cohort of 90 unrelated healthy individuals was analysed by the same methods for presence of common populational polymorphisms, and frequency of five-loci haplotypes was calculated. Linkages of gene aberrations in single SPINK1 gene copies were analysed by long-distance PCR followed by allele-specifi c PCR and DNA sequencing. RESULTS: The most frequent SPINK1 gene mutation N34S was found at a frequency of 6%. Furthermore, we detected the heterozygous intervening sequence (IVS) 3 + 2 T > C mutated gene in 2 German patients and 1 Macedonian chronic pancreatitis patient. In all three SPINK1 gene copies an additional rare base substitution was found: 5’untranslated region (UTR)-215 G > A. Poly-morphism analysis revealed that all three affected genes carried the same fi ve-loci haplotype. DNA sequencing of another chronic pancreatitis-related gene PRSS1 (cationic trypsinogen) did not reveal any mutations in these 3 pa-tients.CONCLUSION: We found in 3 (2%) of 172 chronic pancreatitis patients an IVS3 + 2 T > C SPINK1 gene mutation and a base substitution 5’UTR-215 G > A inthe same gene copy. Most probably the 5’UTR-215 G >A represents a rare polymorphism and not a mutationas previously concluded. Haplotype analysis suggests acommon origin of the IVS3 + 2 T > C mutation in thesepatients.