Colorectal laterally spreading tumors show characteristic expression of cell polarity factors, including atypical protein kinase C λ/ι, E-cadherin, β-catenin and basement membrane component

Ichikawa, Yasushi; Nagashima, Yoji; Morioka, Kaori; Akimoto, Kazunori; Kojima, Yasuyuki; Ishikawa, Takashi; Goto, Ayumu; Kobayashi, Noritoshi; Watanabe, Kazuteru; Ota, Mitsuyoshi; Fujii, Satoshi; Kawamata, Mayumi; Takagawa, Ryo; Kunizaki, Chikara; Takahashi, Hirokazu; Nakajima, Atsushi; Maeda, Shin; Shimada, Hiroshi; Inayama, Yoshiaki; Ohno, Shigeo; Endo, Itaru

doi:10.3892/ol.2014.2271

Cited by 6 publications

(6 citation statements)

References 26 publications

(34 reference statements)

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“…Recent studies are now beginning to elucidate the molecular characteristics of this spatial tumor growth. For example, colorectal tumors that show laterally spreading patterns show unique gene expression features including β-catenin, type IV collagen, and aPKC [ 5 ]. Mathematical modeling of the spatial tumor growth has been often used to explain the process of longitudinal tumor growth [ 6 – 8 ].…”

Section: Introductionmentioning

confidence: 99%

The Clinical Significance and Molecular Features of the Spatial Tumor Shapes in Breast Cancers

et al. 2015

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Each breast cancer has its unique spatial shape, but the clinical importance and the underlying mechanism for the three-dimensional tumor shapes are mostly unknown. We collected the data on the three-dimensional tumor size and tumor volume data of invasive breast cancers from 2,250 patients who underwent surgery between Jan 2000 and Jul 2007. The degree of tumor eccentricity was estimated by using the difference between the spheroid tumor volume and ellipsoid tumor volume (spheroid-ellipsoid discrepancy, SED). In 41 patients, transcriptome and exome sequencing data obtained. Estimation of more accurate tumor burden by calculating ellipsoid tumor volumes did not improve the outcome prediction when compared to the traditional longest diameter measurement. However, the spatial tumor eccentricity, which was measured by SED, showed significant variation between the molecular subtypes of breast cancer. Additionally, the degree of tumor eccentricity was associated with well-known prognostic factors of breast cancer such as tumor size and lymph node metastasis. Transcriptome data from 41 patients showed significant association between MMP13 and spatial tumor shapes. Network analysis and analysis of TCGA gene expression data suggest that MMP13 is regulated by ERBB2 and S100A7A. The present study validates the usefulness of the current tumor size method in determining tumor stages. Furthermore, we show that the tumors with high eccentricity are more likely to have aggressive tumor characteristics. Genes involved in the extracellular matrix remodeling can be candidate regulators of the spatial tumor shapes in breast cancer.

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Section: Introductionmentioning

confidence: 99%

The Clinical Significance and Molecular Features of the Spatial Tumor Shapes in Breast Cancers

et al. 2015

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“…However, PKCζ protein expression patterns showed conflicting results wherein up- or down-regulation was shown in CRACs 15 , 25 . PKCλ expression was up-regulated in CRAC compared with the non-neoplastic epithelia 9 , 16 . PKCζ/λ protein expression was increased in the carcinogen-induced colonic mucosa 28 .…”

Section: Discussionmentioning

confidence: 92%

“…PKCζ/λ exhibited an up-regulation in several cancers, including gastrointestinal tract cancers related with motility and invasiveness 10 - 13 . PKCζ/λ was overexpressed in colon cell lines and showed clinicopathologic significance in colorectal adenocarcinoma (CRAC) 8 , 14 - 16 . CRAC is the most common gastrointestinal cancer and a leading cause of cancer mortality in both men and women 17 .…”

Section: Introductionmentioning

confidence: 99%

Phosphorylated Protein Kinase C (Zeta/Lambda) Expression in Colorectal Adenocarcinoma and Its Correlation with Clinicopathologic Characteristics and Prognosis

et al. 2017

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Background: Protein kinase C zeta/lambda (PKCζ/λ) is a family of protein kinase enzymes that contributes to cell proliferation and regulation, which are important for cancer development. PKCζ/λ has been shown to be an important regulator of tumorigenesis in intestinal cancer. The phosphorylated form of PKCζ/λ, p-PKCζ/λ, is suggested as an active form of PKCζ/λ. However, p-PKCζ/λ expression and its clinicopathologic implication in colorectal adenocarcinoma (CRAC) are unclear.Methods: Seven whole-tissue sections of malignant polyps containing both non-neoplastic and neoplastic mucosa, 11 adenomas with low-grade dysplasia, and 173 CRACs were examined by immunohistochemistry and western blot assay for p-PKCζ/λ protein expression. The association of p-PKCζ/λ expression with clinicopathologic factors including patient survival was studied.Results: In non-neoplastic epithelia, p-PKCζ/λ showed a weak cytoplasmic immunostaining. Adenomas and CRACs demonstrated up-regulated p-PKCζ/λ detection. Cytoplasmic p-PKCζ/λ expression was higher in CRAC than in adenoma. In CRACs, p-PKCζ/λ expression was inversely correlated with pathologic TNM stage (I-II versus III-IV) and poor differentiation. Statistical correlations between low expression of p-PKCζ/λ with shortened overall survival and disease-free survival were seen (p=0.004 and p=0.034, respectively).Conclusions: P-PKCζ/λ overexpression is implicated in tumorigenesis but down-regulation was a poor prognostic factor in CRAC.

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“…We hypothesized that different growth patterns may be one of the visible manifestations of genetic heterogeneity. Similar with breast cancer, colorectal tumors which have a laterally spreading pattern show unique expression features of various genes including β-catenin, type IV collagen, and PKC [15]. If highly proliferative clones are located in one marginal area, they are likely to form ellipsoid tumors and cause more metastasis.…”

Section: Discussionmentioning

confidence: 99%

Growth pattern can be used as a new characteristic to predict malignancy in breast cancer

Wang

Zhu

et al. 2020

Breast Cancer

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Background To date, anatomic tumor length is a key criterion for cancer staging and can be used to evaluate the effectiveness of therapies. This article describes growth pattern that can be used as a new characteristic to represent disease burden and tumor features and predict lymphatic metastasis. Methods Patients with breast cancer were included in this 10-year (1999-2008) hospital-based multicenter retrospective study. The pathologic length/height ratio was used to illustrate the correlation between tumor features, behaviors and treatments in breast malignancies. The most appropriate ratio was chosen based on the comprehensive evaluation of p value and changing trend of each characteristic. Results The sample consisted of 4211 women diagnosed with breast cancer. Among them, 2037 patients with complete pathologic length, width and height information were included in the final analysis. There were 2.34 ± 4.77 metastatic lymph nodes for spheroid tumors and 3.21 ± 5.82 for ellipsoid tumors when the cutoff point was 2. In addition, the proportion of ellipsoidal tumors gradually increased from 54.36 to 56.67% in the upper outer quadrant (UOQ) and from 6.7 to 9.03% in the central region with an increase in the cutoff point. The proportion of ER + PR + ellipsoid tumors significantly decreased from 50.1 to 45.35% and that of ER-PR ellipsoid tumors significantly increased from 32.73 to 36.24% with an increase in the cutoff point. Additionally, the best length/weight ratio to distinguish spheroid and ellipsoid tumors was 2. Conclusion This study described for the first time how growth pattern is correlated with tumor malignancy and how it influences the selection of therapeutic strategies for patients.

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Colorectal laterally spreading tumors show characteristic expression of cell polarity factors, including atypical protein kinase C λ/ι, E-cadherin, β-catenin and basement membrane component

Cited by 6 publications

References 26 publications

The Clinical Significance and Molecular Features of the Spatial Tumor Shapes in Breast Cancers

The Clinical Significance and Molecular Features of the Spatial Tumor Shapes in Breast Cancers

Phosphorylated Protein Kinase C (Zeta/Lambda) Expression in Colorectal Adenocarcinoma and Its Correlation with Clinicopathologic Characteristics and Prognosis

Growth pattern can be used as a new characteristic to predict malignancy in breast cancer

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