Screening of differentially expressed microRNAs in borderline and malignant gastrointestinal stromal tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>Gastrointestinal stromal tumors (GISTs) have a broad spectrum of biological behaviors ranging from benign, borderline and malignant. This study aimed to screen differentially expressed microRNAs (miRNAs) between malignant and borderline GISTs and to investigate the potential role of miRNAs in the malignant transformation of GISTs.</p><p><b>METHODS</b>Six GIST samples including borderline tumors (n = 3) and malignant tumors (n = 3) were collected based on the clinical and pathological characteristics. Total RNA was extracted, followed by miRNA microarray analysis to screen the differentially expressed miRNAs. The most significantly expressed 4 miRNAs were then chosen for further validation by real-time PCR in 22 additional GIST samples.</p><p><b>RESULTS</b>Direct comparison of malignant group versus borderline group revealed 14 significantly and differentially expressed miRNAs (P < 0.05, with a fold change of < 0.5 or > 2). Five miRNAs were up-regulated and nine were down-regulated in the malignant group. Four miRNAs (miR-221, miR-135b, miR-675(*) and miR-218) were most significantly and differentially expressed between the two groups. The differential expression of 2 miRNAs (miR-221 and miR-675(*)) were subsequently confirmed with good concordance by real-time PCR.</p><p><b>CONCLUSIONS</b>The differential miRNA expression profiles between two groups are revealed by miRNA microarray assay, and confirmed by real-time PCR. Among differentially expressed miRNAs, miR-221 and miR-675(*) might be related to the malignant transformation of GISTs, and have a potential value in predicting biological behavior of GISTs.</p>

Detection of KRAS gene mutation and its clinical significance in colorectal adenocarcinoma / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the clinical significance of KRAS mutation detection in colorectal adenocarcinoma.</p><p><b>METHODS</b>Paraffin-embedded tissue specimens were obtained from 440 patients with colorectal adenocarcinoma. The genomic DNA was extracted. Mutations of exon 2 of KRAS gene were examined by PCR and direct sequencing.</p><p><b>RESULTS</b>Somatic mutations of KRAS gene were identified in 146 cases, with the mutation rate of 33.2% (146/440). Among these 146 patients, KRAS mutation involved codon 12 in 118 patients, including 35G > A (Gly12Asp, 62 cases), 35G > T (Gly12Val, 35 cases), 34G > T (Gly12Cys, 9 cases), 34G > A (Gly12Ser, 6 cases), 35G > C (Gly12Ala, 5 cases), and 34G > C (Gly12Arg, 1 case); in 27 patients the mutation involved codon 13, including 38G > A (Gly13Asp, 25 cases), 38G > C (Gly13 Val, 1 case) and 37G > T (Gly13 Cys, 1 case); and in one patient, the mutation involved codon 14 with 40G > A (Val14Ile). The status of KRAS or codon 12 mutations in colorectal adenocarcinoma was related to patients' gender (P = 0.021 and P = 0.030, respectively), and this significant correlation to females was conserved in clinical stage III (P = 0.007 and P = 0.003, respectively), but not in stages I, II, and IV. The status of KRAS or codon 12 mutations was also related to tumor stage. Between stage II and stage IV, the mutation rate of KRAS and codon 12 showed significant difference (P = 0.028 and 0.034, respectively). Between stage III and stage IV, only the codon 12 mutation rate showed significant difference (P = 0.011). Codon 13 mutation was not related to tumor stage.</p><p><b>CONCLUSION</b>About one third of patients with colorectal adenocarcinoma have KRAS gene mutation, which might be related to patients' gender; and could be consistently detected by PCR and direct sequencing.</p>

Staging and histologic grading of gastrointestinal stromal tumors / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinical stage and histological grade of gastrointestinal stromal tumors.</p><p><b>METHODS</b>Twelve clinical and pathological parameters were assessed in 613 patients with follow-up information. These parameters were classified into two gross spread parameters including liver metastasis and peritoneal dissemination, five microscopic spread parameters including lymph node metastasis, vascular, fat, nerve and mucosal infiltration, and five histological parameters including mitotic count ≥ 10 per 50 high-power fields, muscularis propria infiltration, coagulative necrosis, perivascular pattern and severe nuclear atypia.</p><p><b>RESULTS</b>The accumulated 5-year disease-free survival (DFS) and overall survival (OS) of 293 patients without any of these predictive parameters of malignancy were 99.3% and 100.0%, respectively. They were regarded as nonmalignant and further evaluations on the stage and grade of these tumors were not performed. At least one and at most seven predictive parameters of malignancy were identified in 320 patients. For these patients, the accumulated 5-year DFS and OS rates were 43.9% (mean 6.7 years) and 59.7% (mean 9.3 years), respectively. The DFS showed significant difference between patients with and without gross spread (P < 0.01), with and without microscopic spread (P = 0.001). DFS and OS were associated with the number of predictive parameters of malignancy in patients without gross spread (P < 0.01 for both DFS and OS), but not in patients with gross spread (P = 0.882 and 0.441, respectively).</p><p><b>CONCLUSIONS</b>Malignant GIST could be divided into clinical stages I and II based on the absence and presence of gross spread, respectively. The degree of malignancy of patients in clinical stage I could be graded according to the number of predictive parameters of malignancy. Patients in clinical stage II were of the highest degree of malignancy regardless of the number of parameters. The staging and grading of gastrointestinal stromal tumors in this study are strongly associated with prognosis.</p>