Pathological features and clinicopathological significance of TERT promoter mutation in breast fibroepithelial tumors without definite diagnosis / 中华病理学杂志

Objective: To investigate the pathological features and the clinicopathological significance of TERT detection in those tumors that were difficult to diagnosis. Methods: A total of 93 cases of fibroepithelial tumors without definite diagnosis were collected from the Affiliated Hospital of Qigndao University between 2013 and 2021. The clinical details such as patients' age and tumor size were collected. All slides were re-reviewed and the pathologic parameters, including stromal cellularity, stromal cell atypia, stromal cell mitoses, and stromal overgrowth were re-interpreted. Sanger sequencing was used to detect TERT promoter status, and immunohistochemistry was performed to detect TERT protein expression. The relationship between TERT promoter mutation as well as protein expression levels and the clinicopathological parameters were also analyzed. Results: The patients' ages ranged from 30 to 71 years (mean of 46 years); the tumor size ranged from 1.2 to 8.0 cm (mean 3.8 cm). These tumors showed the following morphologic features: leafy structures in the background of fibroadenoma, or moderately to severely abundant stromal cells. The interpretations of tumor border status were ambiguous in some cases. The incidence of TERT promoter mutation was high in patients of age≥50 years, tumor size≥4 cm, and stromal overgrowth at ×4 or ×10 objective, and these clinicopathologic features were in favor of diagnosis of phyllodes tumors. TERT protein expression levels was not associated with the above clinicopathologic parameters and its promoter mutation status. Conclusions: The diagnostic difficulty for the breast fibroepithelial tumors is due to the difficulty in recognition of the leafy structures or in those cases with abundant stromal cells. A comprehensive evaluation combined with morphologic characteristics and molecular parameters such as TERT promoter may be helpful for the correct diagnosis and better evaluating recurrence risk.

Clinicopathological features of rectal adenocarcinoma with enteroblastic differentiation / 中华病理学杂志

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.

Overexpression of catalytic subunit M2 in patients with ovarian cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The formation and growth of tumors are related to the synthesis of the DNA. The enzyme ribonucleotide reductase (RR) is an enzyme that regulates the total rate of DNA synthesis and thus plays a pivotal role in cell growth. Catalytic subunit M2 (RRM2) is the main unit modulating the ribonucleotide reductase enzymatic activity. This study aimed to investigate the expression of RRM2 mRNA and protein in patients with ovarian cancer and its relevance to diagnosis and clinical outcome of the patients.</p><p><b>METHODS</b>RRM2 mRNA levels and protein expression were detected in 98 ovarian specimens with immunohistochemistry and real-time quantitative polymerase chain reaction (PCR). Expression of the RRM2 protein and correlation of the RRM2 gene expression with clinical pathological features were analyzed. The Kaplan-Meier test was used for evaluating RRM2 expression and time to progression and survival. The Cox proportional model was used to analyze the risk factors in prognosis of patients.</p><p><b>RESULTS</b>Positive RRM2 immunostaining was found in 43 of 62 (69.4%) patients with epithelial ovarian cancer, 10 of 15 (66.7%) patients with borderline neoplasm, 4 of 15 (26.7%) patients with benign growths, and none of the normal group. The RRM2 mRNA levels were significantly over expressed in epithelial ovarian cancer (1.722 ± 0.639) and borderline ovarian neoplasms (1.365 ± 0.615), compared to the normal group (0.678 ± 0.446) and benign group (0.828 ± 0.545). Patients with ovarian caner in clinical FIGO-stages III-IV presented higher RRM2 gene expression than those in clinical FIGO-stages I-II. Furthermore, the survival of patients with low RRM2 mRNA level was significantly better than patients with high levels (P < 0.05). By Cox proportional risk model analysis, the risk of mortality of patients with high level expression of RRM2 mRNA was 2.553 times greater than those with low expression.</p><p><b>CONCLUSION</b>RRM2 expression closely correlates with the development of ovarian tumor and may serve as a novel predictive marker for diagnosis and prognosis of the disease.</p>

Differential expression of secretagogin and glucose-related protein 78 in colorectal carcinoma: a proteome study / 中华病理学杂志

<p><b>OBJECTIVE</b>To identify the differentially expressed proteins or peptides and potential biomarkers of tumorigenesis for colorectal cancers.</p><p><b>METHODS</b>Immobilized pH gradient two-dimensional gel electrophoresis (2-DE) was used to separate and obtain the differentially expressed protein spots between colorectal cancers and matched normal mucosa. Liquid chromatography/mass spectrometry (LC-MS/MS) was used to characterize these proteins. Selected candidate proteins were further studied by Western blot, semi-quantitative RT-PCR and immunohistochemical staining.</p><p><b>RESULTS</b>Thirty-five protein spots showed marked expression changes (more than 5-fold) in colorectal carcinoma compared to normal mucosa. Fifteen proteins were up regulated and 20 were down regulated. Fourteen of these proteins were identified by tandem mass spectrometry, among which secretagogin (SCGN) was down-regulated and glucose-related protein (GRP) 78 was up-regulated in the tumors. The SCGN down-regulation was further supported by Western blot and RT-PCR analyses. Immunohistochemistry revealed that SCGN was strongly expressed in neuroendocrine cells of the colonic crypts and 53 of 54 (98%) neuroendocrine tumors. At protein level, although GRP78 was up regulated in colorectal carcinoma, there was no difference in the mRNA expression level between the tumor and paired normal mucosa.</p><p><b>CONCLUSIONS</b>The 2-DE combined with MS is a powerful tool for screening potential tumor biomarkers. The differentially expressed candidate proteins identified by 2-DE may be of significance in understanding the tumorigenesis of the colon cancer. SCGN is a potential biomarker for neuroendocrinal differentiation. GRP78 up-regulation in colorectal carcinomas may be related to its post-translational modification.</p>

The correlation between polymorphisms of matrix metalloproteinase-2 and -9 genes and colorectal cancer of Chinese patients / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate whether the polymorphisms of matrix metalloproteinase-2 (MMP-2) and -9 (MMP-9) promoters contribute to the development and progression of colorectal cancer in Chinese population.</p><p><b>METHODS</b>the PCR-based denaturing high-performance liquid chromatography or PCR-restriction fragment length polymorphism technique respectively was applied to analyze the MMP-2 -1306C/T and MMP-9 -1562C/T polymorphisms in normal group (126 individuals) and colorectal cancer group (126 cases). Genotype frequencies were compared between patients and matched controls, and the association of genotypes with clinical-pathological parameters was studied.</p><p><b>RESULTS</b>The frequency of the CC genotype in the MMP-2 gene polymorphism was significantly increased in colorectal cancer patients when compared with controls (P<0.05), and individuals with the CC genotype had an increased risk of developing colorectal cancer compared to those with CT+TT genotypes (OR: 1.959; 95%CI: 1.055-3.637). Significant correlation was found between the depth of tumor invasion and MMP-2 -1306C/T polymorphism in colorectal cancer patients. However, the genotype frequencies of MMP-9 -1562C/T in colorectal cancer patients were similar to those in control subjects.</p><p><b>CONCLUSION</b>Our results indicate that MMP-2 -1306 C/T polymorphism may be associated with genetic susceptibility to colorectal cancer and the invasive capability of colorectal cancer in Chinese patients. And it is easier for the CC genotype cancer to invade through bowel wall.</p>

Expression of beta-catenin in human colorectal adenoma and carcinoma / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To investigate the expression of beta-catenin and its significance in colorectal neoplasms.</p><p><b>METHODS</b>Tissue specimens of normal colorectal mucosa, mucosa adjacent to carcinoma, colorectal adenoma and adenocarcinoma were examined for beta-catenin with immunohistochemistry.</p><p><b>RESULTS</b>Beta-catenin was mainly expressed in the cytomembrane of normal mucosa and mucosa adjacent to cancer (the positive rates were 94.6% and 86.5%, respectively) and also in the cytoplasm (the positive rates were 38.7% and 55.0%, respectively), while its expression was negative in the cell nucleus. In adenoma and adenocarcinoma, beta-catenin was mainly expressed in the cytoplasm (the positive rates were 85.1%,and 93.7%, respectively) and partially in the cell nucleus (the positive rates were 12.8% and 23.4%, respectively). Compared with normal mucosa and mucosa adjacent to cancer, the expression of beta- catenin in the cytomembrane of adenoma and adenocarcinoma was significantly lower (P<0.05), while its expression in the cytoplasm and cell nucleus of adenoma and adenocarcinoma was significantly higher (P<0.05). The positive rates of cytoplasm in highly-and moderately differentiated adenocarcinoma were significantly higher than that in poorly-differentiated adenocarcinoma (the positive rates were 100%, 95.5% and 68.8%, respectively). Beta-catenin expression rate in cytoplasm was correlated with Dukes'stages of adenocarcinoma, which was significantly lower in stage A than in stage B/C.</p><p><b>CONCLUSION</b>The expression of beta-catenin is significantly correlated with differentiation and Dukes'stages of colorectal carcinoma and it can be used as an indicator for the prognosis of colorectal carcinoma.</p>