Journal of Pathology and Translational Medicine

Case Study

Colorectal adenocarcinoma with enteroblastic differentiation: diagnostic challenges of a rare case encountered in clinical practice: Evi Abada, Ifeoma C. Anaya, Othuke Abada, Anthony Lebbos, Rafic Beydoun; J Pathol Transl Med. 2022;56(2):97-102. Published online January 21, 2022; DOI: https://doi.org/10.4132/jptm.2021.10.28

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Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare subtype of colonic adenocarcinoma characterized by increased α-fetoprotein (AFP) production and the expression of at least one enteroblastic marker including AFP, glypican 3 (GPC3), or Spalt like transcription factor 4 (SALL4). We report a case of a 26-year-old female who presented with low back pain and constipation which persisted despite supportive measures. Imaging revealed multiple liver lesions and enlarged retroperitoneal nodes. Tumor markers including AFP were markedly elevated. On biopsy, samples from the liver revealed infiltrating glands lined by columnar-type epithelium with mostly eosinophilic granular to focally clear cytoplasm. By immunohistochemistry, the tumor showed immunoreactivity with AFP, hepatocyte antigen, GPC3, SALL4, CDX2, SATB2, and cytokeratin 20. A colonoscopy performed subsequently revealed a mass in the sigmoid colon and biopsy of this mass revealed a similar histology as that seen in the liver. A diagnosis of CAED was made, following the results of gene expression profiling by the tumor with next-generation sequencing which identified pathogenic variants in MUTYH, TP53, and KDM6A genes and therefore supported its colonic origin. Cases such as this underscores the use of ancillary diagnostic techniques in arriving at the correct diagnosis in lesions with overlapping clinicopathologic characteristics.

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Hiroshi Minato, Akane Yoshikawa, Sho Tsuyama, Kazuyoshi Katayanagi, Kengo Hayashi, Yusuke Sakimura, Hiroyuki Bando, Tomohiro Hori, Yosuke Kito
International Journal of Surgical Pathology.2023; 31(8): 1553. CrossRef
Beyond liver cancer, more application scenarios for alpha-fetoprotein in clinical practice
Chenyu Ma, Yuexinzi Jin, Yuhan Wang, Huaguo Xu, Jiexin Zhang
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AIEgens assisted label free DNA supersandwich immunoassay for ultrasensitive α-fetoprotein detection
Xiaowen Ou, Jingman Dai, Yiting Huang, Xiaoqin Xiong, Zhi Zheng, Xiaoding Lou, Fan Xia
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Takako Kihara, Ryuichi Kuwahara, Kurando Kusunoki, Tomohiro Minagawa, Yuki Horio, Motoi Uchino, Hiroki Ikeuchi, Seiichi Hirota
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Original Articles

Aurora Kinase A Is a Prognostic Marker in Colorectal Adenocarcinoma: Hyun Min Koh, Bo Geun Jang, Chang Lim Hyun, Young Sill Kim, Jin Won Hyun, Weon Young Chang, Young Hee Maeng; J Pathol Transl Med. 2017;51(1):32-39. Published online December 25, 2016; DOI: https://doi.org/10.4132/jptm.2016.10.17

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Abstract PDF

Background
Aurora kinase A (AURKA), or STK15/BTAK, is a member of the serine/threonine kinase family and plays important roles in mitosis and chromosome stability. This study investigated the clinical significance of AURKA expression in colorectal cancer patients in Korea.
Methods
AURKA protein expression was evaluated by immunohistochemistry in 151 patients with colorectal adenocarcinoma using tissue microarray blocks. We analyzed the relationship between clinicopathological characteristics and AURKA expression. In addition, the prognostic significance of various clinicopathological data for progression-free survival (PFS) was assessed. Also we evaluated copy number variations by array comparative genomic hybridization and AURKA gene amplification using fluorescence in situ hybridization in colorectal carcinoma tissues.
Results
AURKA gene amplification was found more frequently in the 20q13.2–13.33 gain-positive group than the group with no significant gain on the AURKA-containing locus. AURKA protein expression was detected in 45% of the cases (68/151). Positive staining for AURKA was observed more often in male patients (p = .035) and distally located tumors (p = .021). PFS was shorter in patients with AURKA expression compared to those with low-level AURKA expression (p < .001). Univariate analysis revealed that AURKA expression (p = .001), age (p = .034), lymphatic invasion (p = .001), perineural invasion (p = .002), and TNM stage (p = .013) significantly affected PFS. In a multivariate analysis of PFS, a Cox proportional hazard model confirmed that AURKA expression was an independent and significant prognostic factor in colorectal adenocarcinoma (hazard ratio, 3.944; p < .001).
Conclusions
AURKA could serve as an independent factor to predict a poor prognosis in Korean colorectal adenocarcinoma patients.

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The Significance of the Expression of p53, E-cadherin, nm23, CD44, and Tumor Angiogenesis in Colorectal Adenocarcinoma.: Sung Suk Paeng, Hee Jin Chang, Jung Il Suh; Korean J Pathol. 1997;31(4):314-325.

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Abstract PDF: Many oncogenes and tumor supressor genes have been identified and studied in colorectal carcinoma. Among them, p53 is a tumor supressor gene and its mutation is frequently noted in human tumors. E-cadherin is a cell adhesion molecule and associated with tumor differentiation. CD44 is a cell surface glycoprotein that plays a role in cell migration and metastasis. nm23 is a gene known to lower metastatic potential of tumors and has been proposed to be a metastasis supressor gene. Tumor angiogenesis is required for the expansion of the primary tumor and metastasis and its degree is related to the potential of malignancy. We studied the expression of p53, E-cadherin, nm23, CD44 and tumor angiogenesis in 36 cases of colorectal adenocarcinomas. They were compared with previously known prognostic factors such as the stage, tumor size, depth of invasion, differentiation, presence of lymphatic or venous invasion, the lymph node and distant metastasis. The results were as follows. 1) The expression of p53 was not significantly associated with any prognostic factors. 2) The expression of E-cadherin was significantly associated with tumor differentiation. In the well differentiated adenocarcinomas, its expression was higher than in the poorly differentiated adenocarcinoma. 3) The expression of nm23 was also significantly associated with tumor differentiation. In carcinoma with lymph node metastasis, the expression of nm23 was reduced, but statistically it was not significant. 4) The expression of CD44 was higher in tumors with lymph node metastasis than in tumors without lymph node metastasis, but it was not statistically significant. 5) The degree of microvessel density was significantly associated with lymphatic invasion. According to the above results, the expression of E-cadherin and nm23 are related to the differentiation of the tumor and tumor angiogenesis is related to the lymphatic invasion of the colorectal adenocarcinoma.

Expression of p27Kip1 Protein in Colorectal Adenocarcinoma.: Hyang Im Lee, Duck Hwan Kim, Eun Sook Nam, Hye Rim Park, Seoung Wan Chae, Chul Jae Park, Jeong Rye Kim, Hyung Sik Shin; Korean J Pathol. 2000;34(2):132-137.

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Abstract PDF: p27Kip1 has been recognized as a negative regulator of cell cycle. Reduced level of p27 expression is associated with development and aggressiveness of several human tumors. To investigate the role of p27Kip1 on progression of colorectal adenocarcinoma, we studied 40 cases of human colorectal adenocarcinomas for expression of p27Kip1 protein using an immunohistochemical method, and compared these results with known prognostic parameters of colorectal adenocarcinoma. Among 40 cases of colorectal adenocarcinomas, p27Kip1 expression was detected in the nuclei of tumor cells in 14 cases (35%). The expression rate of p27Kip1 protein was significantly lower in the cases with lymph node metastasis (25.8%) than in those without lymph node metastasis (66.6%) (p<0.05). But it did not correlate with other parameters such as tumor size, histologic grade, vascular invasion, and Ki-67 labeling index. The results suggest that reduced expression of p27Kip1 protein plays a role in biologically aggressive behavior of colorectal adenocarcinoma.

Correlation of Expression of E-Cadherin, alpha-Catenin, beta-Catenin, and Clinicopathologic Parameters in Colorectal Adenocarcinomas.: Hyoung Joong Kim, Tae Jin Lee, Eon Sub Park, Jae Hyung Yoo; Korean J Pathol. 2000;34(4):264-272.

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Abstract PDF: The E-cadherin, alpha-catenin, and beta-catenin expressions were immunohistochemically investigated in paraffin-embedded materials of 80 cases of colorectal adenocarcinomas. The staining similar to normal colorectal mucosa with preserved strong membranous staining pattern was considered normal or preserved expression. The X2 test was used to analyse the statistical correlation of cadherin/catenin expression with clinicopathologic parameters and the Breslow test for the correlation with survival length. Normal colorectal mucosa showed strong membranous expression of cadherin/catenin complex. The reduced E-cadherin, alpha-catenin, and beta-catenin expression were found in 53/80 (66.3%), 46/80 (57.5%), and 44/80 (55.5%) cases of colorectal cancers examined, respectively. There were significant correlations between E- cadherin and alpha -catenin (p=0.035), and between alpha-catenin and beta-catenin (p=0.013). The reduced E-cadherin expression was associated with histologic dedifferentiation, tumor depth, lymph node metastasis, clinical stage (p<0.05), poor clinical outcome in stage II (p=0.016) and the reduced alpha-catenin expression with lymph node metastasis and clinical stage (p<0.05). Reduced expression of two or more proteins was correlated with lymph node matastasis, histologic dedifferentiation, clinical stage, and survival (p<0.05). The present study demonstrates a significant down-regulation of E-cadherin and alpha-catenin expression in colorectal cancer is associated with tumor invasiveness, histologic dedifferentiation, lymph node metastasis, and clinical stage. These results suggest that E-cadherin and alpha-catenin may be useful markers of invasiveness, lymph node metastatic potential, and clinical stage and of value as prognostic markers in the earlier stage. Further studies are needed to confirm the prognostic value of these cadherin/catenin complex.

Expression of p53 and Matrix Metalloproteinase-2 Proteins in Colorectal Adenocarcinoma.: Seong Jin Cho, Hwa Eun Oh, Yang Seok Chae; Korean J Pathol. 2000;34(7):494-500.

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Abstract PDF: The p53 gene is believed to play an important role through the mutation and overexpression in the progression of various human malignant tumors. The type IV collagenase (matrix metalloproteinase: MMP-2) initiates the degradation of the extracellular matrix, and consequently may play a role in the tumor invasion and metastasis. To investigate the correlation between clinicopathologic features of the colorectal adenocarcinomas and benign tumors and expression of p53 and MMP-2 proteins, we performed an immunohistochemical study on 40 colorectal adenocarcinomas, 20 adenomas and 20 hyperplastic polyps by using the antibodies to p53 and MMP-2 proteins. The positive expression rate of the p53 protein in adenocarcinomas was 62.5% and significantly higher than in benign tumors. The positive expression rate of the MMP-2 protein was 47.5% in adenocarcinomas, but there was no expression of MMP-2 protein in benign tumors. The difference in p53 and MMP-2 expression rates between malignant and non-malignant tumors was statistically significant. The positive expression rate of p53 protein in the non-metastatic and metastatic adenocarcinomas was 59.1 and 66.7%, respectively. The positive expression rate of MMP-2 protein in the non-metastatic and metastatic adencarcinomas was 45.5 and 50.0%, respectively. The correlation between several clinicopathologic features and expression of p53 and MMP-2 protein was not statistically significant, but the rate of positive MMP-2 immunoreactivity showed a statistically significant difference between Astler-Coller stage B1 C1 group and B2 C2 group of adenocarcinoma (p=0.0431). We concluded that the expression of p53 and MMP-2 protein contributes to the cancer development and MMP-2 may play a certain role in the invasiveness of the colorectal tumor. p53 and MMP-2 protein expression is not correlated with lymph node metastasis.

Expression of Chromogranin A, Cathepsin D, Cyclin D1 and p53 proteins in Colorectal Adenocarcinoma.: Chae Hong Suh, Mi Ja Lee, Sung Kang Cho; Korean J Pathol. 2001;35(1):7-13.

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Abstract PDF: BACKGROUND
The purpose of this study is to assess the roles of chromogranin A, cathepsin D, cyclin D1 and p53 protein expression in colorectal tumorigenesis.
METHODS
83 colorectal cancer and 12 villotubular adenoma tissue specimens were investigated by immunohistochemical staining for chromogranin A, cathepsin D, cyclin D1 and p53 protein. Clinicopathologic values (tumor size, histologic grade, Astler-Coller stage and lymph node metastasis) were compared with the incidence of chromogranin A, cathepsin D, cyclin D1 and p53 protein expression in colorectal adenocarcinomas.
RESULTS
Statistically significant correlation was noted between the expression of chromogranin A and histologic grade (p<0.05). The incidence of positive cathepsin D expression was increased with tumor size (p<0.05), and there was a statistically significant correlation between histologic grade and cathepsin D expression (p<0.005). There were no statistically significant correlations among cyclin D1 expression and tumor size, histologic grade, stage and lymph node metastasis. Patients with lymph node metastasis had a high incidence of positive p53 protein expression compared to those without this finding (p<0.001).
CONCLUSION
It is suggested that chromogranin A, cathepsin D, and p53 protein are useful variables for the prognostic assessment of colorectal adenocarcinoma. The p53 protein seems to involve the metastatic ability of colorectal adenocarcinomas. Also, the expression of cathepsin D, cyclin D1, and p53 protein may play an important role in the tumorigenesis and progression of the colorectal adenoma-carcinoma sequence.

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