PURPOSE: To investigate the association of cancer stem-cell markers [octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), and Nanog homebox (NANOG)] expression with clinicopathological properties and overall survival (OS) in operative rectal cancer (RC) patients receiving adjuvant therapy. MATERIALS AND METHODS: 153 patients with primary RC receiving surgery were enrolled. Tumor tissue and paired adjacent normal tissue sample were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunofluorescent staining. The median follow-up duration was 5.2 years, and the last follow-up date was August 2016. RESULTS: Tumor tissue OCT4 (p < 0.001), SOX2 (p=0.003), and NANOG (p < 0.001) expressions were higher than those in adjacent tissue. OCT4 expression was positively correlated with pathological grade (R=0.185, p=0.022), tumor size (R=0.224, p=0.005), and N stage (R=0.170, p=0.036). NANOG expression was positively associated with tumor size (R=0.169, p=0.036). Kaplan-Meier suggested that OCT4+ was associated with worse OS compared with OCT4− (p < 0.001), while no association of SOX2 (p=0.121) and NANOG expressions (p=0.195) with OS was uncovered. Compared with one or no positive marker, at least two positive markers were associated with shorter OS (p < 0.001), while all three positive markers were correlated with worse OS compared with two or less positive markers (p < 0.001). Multivariate Cox's analysis revealed that OCT4+ (p < 0.001) and N stage (p=0.046) were independent factors for shorter OS. CONCLUSION: Tumor tissue OCT4 expression was correlated with poor differentiation, tumor size, and N stage, and it can serve as an independent prognostic biomarker in operative patients with RC receiving adjuvant therapy.
Aged ; Biomarkers, Tumor/metabolism ; Female ; Humans ; Male ; Multivariate Analysis ; Nanog Homeobox Protein/metabolism ; Neoplastic Stem Cells/metabolism ; Octamer Transcription Factor-3/metabolism ; Prognosis ; Rectal Neoplasms/metabolism ; Rectal Neoplasms/pathology ; Rectal Neoplasms/surgery ; SOXB1 Transcription Factors/metabolism ; Survival Analysis

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

Adenocarcinoma ; metabolism ; pathology ; Aged ; Carcinoid Tumor ; metabolism ; pathology ; Chromogranin A ; metabolism ; Humans ; Immunohistochemistry ; Male ; Neoplasms, Multiple Primary ; metabolism ; pathology ; Phosphopyruvate Hydratase ; metabolism ; Rectal Neoplasms ; metabolism ; pathology ; S100 Proteins ; metabolism

No abstract available.
Carcinoid Tumor/*diagnosis ; Female ; Humans ; Ki-67 Antigen/*metabolism ; Male ; Rectal Neoplasms/*diagnosis

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 ; MicroRNAs/metabolism* ; Neoplasm Recurrence, Local ; Rectal Neoplasms/pathology* ; Neoadjuvant Therapy ; Radiation Tolerance/genetics*

Breast Neoplasms ; metabolism ; pathology ; surgery ; Carcinoma, Lobular ; metabolism ; pathology ; secondary ; surgery ; Carrier Proteins ; metabolism ; Female ; Glycolipids ; metabolism ; Glycoproteins ; metabolism ; Humans ; Mastectomy, Modified Radical ; Middle Aged ; Rectal Neoplasms ; secondary

OBJECTIVETo determine the association of CD133 expression with the sensitivity to radiotherapy among rectal cancer patients.

METHODSThe clinical data of 32 rectal cancer patients was retrospectively collected for patients who received a short-term preoperative radiotherapy(5 Gy/d,×5 d) from 2008 to 2010. Pretreatment tumor biopsies were immunostained for CD133 expression. Rectal cancer regression grade (RCRG) was used to evaluate the sensitivity of the rectal cancer to preoperative radiotherapy. The correlation of CD133 expression and sensitivity to radiotherapy was analyzed.

RESULTSCD133 differentially expressed in rectal cancer tissue with 17 high expression and 15 low expression. The expression of CD133 was associated with the differentiation of rectal cancer with higher expression of CD133 among poorly differentiated rectal cancers(P<0.05). Among the CD133-high patients, two patients showed 1st RCRG, five patients showed 2nd RCRG and ten patients showed 3rd RCRG. For the CD133-low patients, there were five 1st RCRG, seven 2nd RCRG and three 3rd RCRG. There was a significant association between CD133 expression and sensitivity to radiotherapy (P=0.037). Multivariate logistic regression analysis showed that the expression level of CD133(P=0.027) and the differentiation of rectal cancer(P=0.046) were independent predictive factors for the sensitivity of rectal cancer to radiotherapy.

CONCLUSIONSCorrelation between CD133 expression and sensitivity to radiotherapy of rectal cancer may exist, which may be helpful in predicting the sensitivity of rectal cancer to preoperative radiotherapy.

AC133 Antigen ; Antigens, CD ; metabolism ; Biomarkers, Tumor ; metabolism ; Biopsy ; Combined Modality Therapy ; Glycoproteins ; metabolism ; Humans ; Peptides ; metabolism ; Rectal Neoplasms ; metabolism ; radiotherapy ; Retrospective Studies

OBJECTIVETo study the morphologic and immunohistochemical features of gastrointestinal stromal tumors (GISTs) and to explore the reference parameters for malignancy.

METHODSSeventy six (76) cases of primary GISTs were distinguished from a group of gastrointestinal mesenchymal tumors by use of a panel of antibodies such as CD117, CD34 by immunohistochemical EnVision method, their biologic behaviors were analyzed by including their follow-up data.

RESULTSAll patients were adults, age range 32 to 81 years (mean 54 year), male 39 cases and female 37 cases; the tumors were situated in stomach (36 cases), in small intestine (23 cases), colon (2 cases) and rectum (15 cases). The most common symptoms were abdomen mass, vague pain and GI bleeding. Forty eight (48) cases were mainly located within the muscularis propria, 25 cases outside the serosa, and 3 cases below the mucosa. Grossly, they were of soft consistency often with hemorrhage, cystification or necrosis. Microscopically, the tumors were composed of spindle cells (46 cases) or epithelioid cells (9 cases) and of both cells (21 cases), arranged in interlacing fasicles, diffusing sheets, pallisading, whirling, alveolar and giant pseudo-rosette shapes. Tumor cells often had abundant cytoplasm with light to moderate eosinophilic or slight basophilic in staining, the nuclei generally showed spindle, blunted ends, round or signet in shape with nucleoli. Immunohistochemically, CD117 and CD34 showed diffuse strong expression, the positive rates were 98.7% and 68.4% respectively, alpha-SMA, MSA, S-100, PGP9.5 showed focal expression, the positive rates were 25.0%, 19.7%, 23.7% and 17.1% respectively, vimentin were all positive and desmin, GFAP, NF were all negative. Nine cases were benign, 19 cases borderline and 48 cases malignant. Follow-up of 20 cases with benign and borderline tumors found patients alive without tumor. In the malignant group of 34 cases, 10 cases were alive without tumor, 10 cases developed recurrence or metastasis, and 14 cases died of tumor. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity and obvious pleomorphism were all in the malignant group. In this group, tumor necrosis, adhesion in operation, tumor, over 5 cm in diameter, mitotic activity over 5/50HPF had significant differences among three groups and the 3 years survival rate had a significant difference in tumors with or without coagulative necrosis and also in tumors with or without mitotic activity over 5/50HPF.

CONCLUSIONSGISTs predominantly occurred in middle aged or old patients, the tumors had varied cell types and different arrangements, the immunohistochemical characters were positive for CD117 and CD34, negative for desmin, occasional positive for alpha-SMA, MSA, S-100 and PGP9.5, which were helpful to differentiate GIST from leiomyomas and Schwannomas. Coagulative necrosis, mitotic activity over 10/50HPF, high cellularity with obvious pleomorphism were also helpful parameters for diagnosis of malignancy aside from metastasis and invasion. Adhesion, over 5 cm in diameter and mitotic activity over 5/50HPF but less than 10/50HPF might be the potential malignant parameters.

Adult ; Aged ; Aged, 80 and over ; Biomarkers, Tumor ; Colonic Neoplasms ; metabolism ; pathology ; Female ; Gastrointestinal Neoplasms ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Intestinal Neoplasms ; metabolism ; pathology ; Male ; Middle Aged ; Rectal Neoplasms ; metabolism ; pathology ; Statistics as Topic ; Stomach Neoplasms ; metabolism ; pathology

OBJECTIVETo investigate the expression of COX-2 and BCL-2 in transitional mucosa adjacent to rectal carcinoma, and to determine whether precursor event exists in the transitional mucosa.

METHODSMucin histochemical method (HID/AB) was used to determine the distal mucosa 2 cm away from rectal carcinoma in 54 patients with rectal cancer. Immunohistochemical method was employed to detect the expression of BCL-2 and COX-2 in the rectal cancer specimen, transitional mucosa (TM), non-transitional mucosa (NTM), and 20 cases of normal rectal mucosa. Student's t-test and Chi-square test were preformed.

RESULTSNineteen patients with positive TM were found. COX-2 expression was identified in 81.5% of cancer tissue, 21.1% of TM, 17.1% of NTM, and 10.0% in normal mucosa. BCL-2 protein was found in 77.8% of cancer tissue, 21.1% of TM, 22.9% of NTM, and 5.0% of normal mucosa. The expressions of COX-2 and BCL-2 in TM were significantly different from tumor tissue[(0.737±0.895) versus (3.519±1.998), and (0.632±0.955) versus (2.833±1.756), all P<0.01]. However, there were no significant differences between TM and NTM or normal mucosa.

CONCLUSIONSExpressions of COX-2 and BCL-2 are non-specific in the transitional mucosa at the distal rectum. Evidence is not available in TM being precursor lesion.

Adult ; Aged ; Cyclooxygenase 2 ; metabolism ; Female ; Humans ; Intestinal Mucosa ; metabolism ; pathology ; Male ; Middle Aged ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rectal Neoplasms ; metabolism ; pathology

Adenocarcinoma ; metabolism ; pathology ; surgery ; Aged ; Humans ; Intestinal Neoplasms ; metabolism ; pathology ; surgery ; Intestine, Small ; Ki-1 Antigen ; metabolism ; Lymphoma, Large B-Cell, Diffuse ; metabolism ; pathology ; surgery ; Male ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Rectal Neoplasms ; metabolism ; pathology ; surgery