2.Clinicopathological features of rectal adenocarcinoma with enteroblastic differentiation.
J LIU ; X L LIU ; D L LIN ; H ZHAO ; Y J LI ; X M XING
Chinese Journal of Pathology 2023;52(8):797-801
Objective: To investigate the clinicopathological features, immunophenotype, and genetic alterations of rectal adenocarcinoma with enteroblastic differentiation. Methods: Four cases of rectal adenocarcinoma with enteroblastic differentiation were collected at the Affiliated Hospital of Qingdao University, Qingdao, China (three cases) and Yantai Yeda Hospital of Shandong Province, China (one case) from January to December 2022. Their clinical features were summarized. Hematoxylin and eosin stain and immunohistochemical stain were performed, while next-generation sequencing was performed to reveal the genetic alterations of these cases. Results: All four patients were male with a median age of 65.5 years. The clinical manifestations were changes of stool characteristics, bloody stools and weight loss. All cases showed mixed morphology composed of conventional adenocarcinoma and adenocarcinoma with enteroblastic differentiation. Most of the tumors consisted of glands with tubular and cribriform features. In one case, almost all tumor cells were arranged in papillary structures. The tumor cells with enteroblastic differentiation were columnar, with relatively distinct cell boundaries and characteristic abundant clear cytoplasm, forming fetal gut-like glands. Immunohistochemically, the tumor cells were positive for SALL4 (4/4), Glypican-3 (3/4) and AFP (1/4, focally positive), while p53 stain showed mutated type in 2 cases. The next-generation sequencing revealed that 2 cases had TP53 gene mutation and 1 case had KRAS gene mutation. Conclusions: Rectal adenocarcinoma with enteroblastic differentiation is rare. It shows embryonal differentiation in morphology and immunohistochemistry, and should be distinguished from conventional colorectal adenocarcinoma.
Humans
;
Male
;
Aged
;
Female
;
Biomarkers, Tumor/metabolism*
;
Adenocarcinoma/pathology*
;
Colorectal Neoplasms
;
Rectal Neoplasms/genetics*
;
Cell Differentiation
3.Mechanisms of microRNA action in rectal cancer radiotherapy.
Lili ZHU ; Mojin WANG ; Na CHEN ; Yujie ZHANG ; Tao XU ; Wen ZHUANG ; Shuomeng XIAO ; Lei DAI
Chinese Medical Journal 2022;135(17):2017-2025
Preoperative neoadjuvant chemoradiotherapy, combined with total mesorectal excision, has become the standard treatment for advanced localized rectal cancer (RC). However, the biological complexity and heterogeneity of tumors may contribute to cancer recurrence and metastasis in patients with radiotherapy-resistant RC. The identification of factors leading to radioresistance and markers of radiosensitivity is critical to identify responsive patients and improve radiotherapy outcomes. MicroRNAs (miRNAs) are small, endogenous, and noncoding RNAs that affect various cellular and molecular targets. miRNAs have been shown to play important roles in multiple biological processes associated with RC. In this review, we summarized the signaling pathways of miRNAs, including apoptosis, autophagy, the cell cycle, DNA damage repair, proliferation, and metastasis during radiotherapy in patients with RC. Also, we evaluated the potential role of miRNAs as radiotherapeutic biomarkers for RC.
Humans
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MicroRNAs/metabolism*
;
Neoplasm Recurrence, Local
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Rectal Neoplasms/pathology*
;
Neoadjuvant Therapy
;
Radiation Tolerance/genetics*
5.Microsatellite instability of sporadic colorectal carcinomas and its clinicopathological significance.
Xiu-ying XIAO ; Xiao-yan ZHOU ; Meng-hong SUN ; Ge YAN ; Xiang DU
Chinese Journal of Oncology 2006;28(4):289-293
OBJECTIVETo investigate the incidence of microsatellite instability (MSI) in sporadic colorectal carcinoma (CRC) using BAT-25 and BAT-26 loci, and its association with clinicopathological features.
METHODSMicrosatellite analysis was performed on tissue samples from 73 primary and 53 metastatic tumors collected at the Department of Pathology, Fudan University Cancer Hospital in 2002. Genomic DNA was extracted from paraffin-embedded tissues. Microsatellite alterations of BAT-25 and BAT-26 were detected using fluorescent PCR followed by fragment analysis on automatic DNA sequencer with GeneScan 3.1 software. A case of hereditary nonpolyposis colorectal cancer syndrome (HNPCC) with known high-frequency MSI (MSI-H) was included as positive control.
RESULTSEleven out of 73 samples from primary tumors (15.1%) were MSI-positive and significantly associated with patient age, tumor site, differentiation and prognosis (P < 0.05). There was no significant difference between the positive rate of MSI in tissue samples from primary and metastatic sites among the 53 metastatic tumors, being 17.0% and 13.2%, respectively, P > 0.05. Two cases with negative MSI at the primary site but positive at the metastatic sites were observed.
CONCLUSIONMSI is a frequent molecular event that may serve as a useful parameter for studying tumor biological behavior. MSI plays a partial role in the metastasis of sporadic CRC, but the role of mismatch repair genes and its exact mechanism remains to be determined. The classification of sporadic CRC according to MSI may be of importance both theoretically and practically.
Adenocarcinoma ; genetics ; secondary ; Adult ; Aged ; Colonic Neoplasms ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; Female ; Follow-Up Studies ; Humans ; Liver Neoplasms ; genetics ; secondary ; Male ; Microsatellite Repeats ; Middle Aged ; Prognosis ; Rectal Neoplasms ; genetics ; pathology
6.The detection of microsatellite instability by ion-pair reversed-phase high performance liquid chromatography.
Xiao-rong LIU ; Ya-ping WANG ; Jun-ni ZHANG ; Jin-tian LI ; Xiao-mei ZHANG ; Ming ZHU ; Xiang-nian SHAN
Chinese Journal of Medical Genetics 2004;21(1):56-60
OBJECTIVETo set up a sensitive and stable technique which has high throughout to detect the instability of microsatellite DNA.
METHODSGenomic DNA extracted from the cancer tissues and their normal tissues were subjected to microsatellite instability(MSI) analysis on five of DNA markers in 115 sporadic colorectal cancers by means of PCR and ion-pair reversed-phase high performance liquid chromatography. Genomic DNA extracted from lymphocytes in blood of 20 normal persons were analysed and used as the standard control.
RESULTSSeventeen (14.8%) MSI-H and 23(20.0%) MSI-L were found in 115 sporadic colorectal cancers. The rates of MSI in the young patients and old patients were much higher than that in the middle-age patients (P<0.05). And the rate of MSI in low differentiation group was also much higher than that in high or middle differentiation groups (P<0.05).
CONCLUSIONThe method the authors developed is a sensitive and accurate technique to detect MSI and has a high throughput.
Adult ; Chromatography, High Pressure Liquid ; methods ; Colonic Neoplasms ; genetics ; pathology ; Colorectal Neoplasms, Hereditary Nonpolyposis ; genetics ; pathology ; DNA, Neoplasm ; analysis ; genetics ; Humans ; Loss of Heterozygosity ; Microsatellite Repeats ; genetics ; Middle Aged ; Rectal Neoplasms ; genetics ; pathology ; Reproducibility of Results ; Sensitivity and Specificity
7.The expression of the apoptosis-suppressive gene bcl-2 in the tissue of colon carcinoma.
Journal of Huazhong University of Science and Technology (Medical Sciences) 2002;22(3):218-220
The role of bcl-2 in the pathogenesis of colorectal tumor were studied. The expression of bcl-2 in the colorectal carcinoma and incisional edge tissue of tumor was detected by using SABC method. The results showed that the positive rate of bcl-2 was 69.6% in colorectal carcinoma and 47.6% in the incisional edge tissue respectively, with the difference being very significant (P = 0.001). Bcl-2 positive rate was associated with Dukes' stage, but had nothing to do with histological classification. It was concluded that bcl-2 might play a significant role in the development of colorectal carcinoma.
Adenocarcinoma
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genetics
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pathology
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Adult
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Apoptosis
;
genetics
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Colonic Neoplasms
;
genetics
;
pathology
;
Female
;
Humans
;
Male
;
Middle Aged
;
Neoplasm Staging
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Proto-Oncogene Proteins c-bcl-2
;
biosynthesis
;
genetics
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Rectal Neoplasms
;
genetics
;
pathology
8.K-ras mutations in rectal cancer undergone preoperative radiotherapy.
Che CHEN ; Fu-kun LIU ; Xiao-ping QI ; Zhe XU ; Guo-li LI ; Jie-shou LI
Chinese Journal of Surgery 2005;43(11):710-712
OBJECTIVETo detect K-ras mutations in rectal carcinoma before and after preoperative radiotherapy, and study genetics effect of radiotherapy in rectal cancer.
METHODSForty patients with rectal cancer in pTNM stage II or III were enrolled. There were 20 males and 20 females. Sixteen tumours were pTNM II stage, 24 pTNM III. All patients received preoperative adjuvant radiotherapy. The treatment time is 4 weeks for 40 Gy in 2.0 Gy fractions and it is usually followed by an interval of 1-2 weeks before the operation. Tumor tissue and normal mucosa 2, 4, 6 cm to tumor were collected from patients before preoperative adjuvant radiotherapy and after operation. The K-ras mutations in codon 12 were investigated using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) in tumors and normal mucosa.
RESULTSThe frequencies of K-ras mutations before preoperative adjuvant radiotherapy in tumor tissue and normal mucosa 2, 4, 6 cm to tumor were 47.5%, 22.5%, 2.5% and 0. The frequencies of K-ras mutations before preoperative adjuvant radiotherapy were higher in tumor tissue than in normal mucosa, and were higher in normal mucosa 2 cm to tumor than 4 cm and 6 cm to tumor. The postoperative frequencies of K-ras mutations in tumor tissue and normal mucosa 2 cm, 4 cm, 6 cm to tumor were 25.0%, 5.0%, 0 and 0. Compared to same locations of control group, the frequency of K-ras mutations in tumor tissue and normal mucosa 2 cm to tumor significantly decreased after radiotherapy.
CONCLUSIONFrequency of K-ras mutations of rectal cancer issue and normal mucosa 2 cm to tumor were significantly higher than other normal rectal mucosa, and decreased significantly after radiotherapy. So radiotherapy can inhibit early events of carcinogenesis of mucosa nearby tumor. It was the potential reason of increased rates of resection and sphincter-saving after radiotherapy.
Adult ; Aged ; DNA Mutational Analysis ; Female ; Genes, ras ; genetics ; Humans ; Male ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; Rectal Neoplasms ; genetics ; pathology ; radiotherapy ; surgery
9.Comparative Evaluation of the Value of Quantitative Parameters of Dual-energy CT and MRI for KRAS Mutation in Rectal Cancer.
Xiao-Qiang LIN ; Tao HAN ; Meng-Yuan JING ; Liang-Na DENG ; Bin ZHANG ; Jun-Lin ZHOU
Acta Academiae Medicinae Sinicae 2022;44(4):606-613
Objective To evaluate and compare the value of quantitative parameters of preoperative dual-energy CT and MRI on KRAS mutation in rectal cancer,and to explore the correlations between postoperative pathological indicators and KRAS mutation. Methods This study retrospectively analyzed 50 patients with rectal cancer confirmed by surgery and pathology and receiving KRAS genetic testing in Lanzhou University Second Hospital from August 2017 to April 2021.According to the results of genetic testing,the patients were assigned into a wild-type group (29 patients) and a mutant type group (21 patients).The preoperative baseline data included sex,age,and serum tumor markers,and the postoperative pathological data included pathological stage,lymphovascular invasion,perineural invasion,and lymph node metastasis.The quantitative parameters of three-phase energy spectral CT included iodine (water) concentration,water (iodine) concentration,effective atomic number,and normalized iodine concentration.The quantitative parameters of apparent diffusion coefficient (ADC) included minimum ADC,average ADC,and relative ADC.In addition,the width of the superior rectal vein was obtained from the CT images of the venous phase,and the tumor segmentation,the maximum axial length of tumor,and the maximum longitudinal length of tumor were obtained from the MRI images.The qualitative and quantitative data were compared by χ2 test,t-test,and Mann-Whitney U test.The diagnostic efficacy of the two detection methods for KRAS mutations in rectal cancer was compared,and the receiver operating characteristic curve was employed to evaluate the diagnostic efficacy. Results The KRAS mutation rate was higher in the carbohydrate antigen 199 abnormal group than the normal group (P=0.036) and higher in the positive group of lymphovascular invasion (P=0.034).The KRAS mutant type group had higher normalized iodine concentration in the venous phase (P=0.016) and lower average ADC and relative ADC (P=0.008, P=0.002,respectively) than the wild-type group.Among them,relative ADC had the highest diagnostic efficiency (AUC=0.755). Conclusion The quantitative parameters of dual-energy CT and ADC have similar diagnostic efficiency for KRAS mutation in rectal cancer,and relative ADC is superior to other parameters.
Humans
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Iodine
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Magnetic Resonance Imaging
;
Mutation
;
Proto-Oncogene Proteins p21(ras)/genetics*
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Rectal Neoplasms/genetics*
;
Retrospective Studies
;
Tomography, X-Ray Computed/methods*
;
Water
10.Relationship between Expression of Runt-related Transcription Factor 3 and Enhancer of zeste Homolog 2 Proteins and Sensitivity to Neoadjuvant Chemotherapy in Locally Advanced Rectal Cancer.
Ze-Long YUAN ; Xue-Liang WU ; Ming QU ; Jun XUE ; Lei HAN ; Guang-Yuan SUN
Acta Academiae Medicinae Sinicae 2021;43(6):856-864
Objective To investigate the expression and correlation of Runt-related transcription factor 3(RUNX3)and enhancer of zeste homolog 2(EZH2)in rectal cancer,and to reveal the relationship between the expression of RUNX3 and EZH2 and the sensitivity of XELOX regimen to neoadjuvant chemotherapy in locally advanced rectal cancer patients. Methods The carcinoma and paracancerous tissues of 31 patients with rectal adenocarcinoma and no preoperative antitumor therapy were selected as cancer group and paracancer group,respectively.The relative mRNA levels of RUNX3 and EZH2 in the two groups were measured by real-time quantitative reverse transcription-polymerase chain reaction,and the protein levels were determined by immunohistochemical assay.The expression of RUNX3 and EZH2 was compared between cancer tissue and paracancerous tissue.The pre-treatment wax blocks of 26 patients with locally advanced rectal cancer who received 3 cycles of XELOX regimen as neoadjuvant chemotherapy before surgery were selected as the pre-neoadjuvant therapy group,and the postoperative pathological wax blocks were selected as the post-neoadjuvant treatment group.Tumor regression grade(TRG)was determined to evaluate the efficacy of neoadjuvant therapy.Immunohistochemical assay was used to detect the protein levels of RUNX3 and EZH2 in the two groups,and then the relationship between the expression patterns of the two proteins and the efficacy of neoadjuvant chemotherapy was analyzed. Results Compared with paracancerous tissue,the cancer tissue showed down-regulated mRNA level and reduced positive protein expression rate of RUNX3,while up-regulated mRNA level(
Core Binding Factor Alpha 3 Subunit/genetics*
;
Enhancer of Zeste Homolog 2 Protein/genetics*
;
Humans
;
Neoadjuvant Therapy
;
Rectal Neoplasms/drug therapy*
;
Transcription Factor 3