Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2022

Open Access 01-12-2022 | Oral Cancer | Research

Expressional variations of Kaiso: an association with pathological characteristics and field cancerization of OSCC

Authors: Shaheen Ahmed, Saeed Khan, Muhammad Asif Qureshi, Uzma Bukhari, Mehak Anis, Muhammad Nouman Mughal

Published in: BMC Cancer | Issue 1/2022

Login to get access

Abstract

Background

A group of genetically altered cells that have not transformed into a clinical or histologically identifiable state of malignancy but contains a higher risk of transforming into one is known as the field of cancerization. Numerous molecules are being investigated for their significance in the development of this phenomenon. One such protein of this family is Kaiso also known as ZBTB33 (Zinc Finger and BTB Domain containing 33). This protein belongs to the POZ-ZF family of transcription factors and may have functional tasks similar to its other siblings such as the growth and development of vertebrates and the pathogenesis of neoplastic diseases. Nevertheless, its role in the pathogenesis, progression, epithelial mesenchyal transition and field cancerization in case of oral cancer still needs exploration. Hence, this study was designed to explore the expressional differences between the mucosa of controls and those diagnosed with oral squamous cell carcinoma (OSCC).

Methods

Soft tissue samples were obtained from the main tumor, tumor periphery and opposite buccal mucosa of 50 oral cancer patients, whereas normal mucosa was taken from 50 volunteers undergoing elective tooth removal. The acquired samples were subjected to Immunohistochemical exploration for expression of Kaiso and E-Cadherin. The expression was measured using Image-J IHC profiler and summed as Optical density. The Optical density values were then subjected to statistical analysis.

Results

Results revealed a significant differential expression of Kaiso between the mucosal tissues taken from oral cancer patients and controls (p-value: < 0.0001), showing almost 50% down-regulation of Kaiso in all three tissue samples taken from oral cancer patients as compared to normal mucosa.

Conclusion

Kaiso has a significant difference of expression in the mucosa of oral cancer patients as compared to the mucosa of normal patients, making it a probable contributor to disease pathogenesis and field cancerization.
Appendix
Available only for authorised users
Literature
1.
Eljabo N, Nikolic N, Carkic J, Jelovac D, Lazarevic M, Tanic N, et al. Genetic and epigenetic alterations in the tumour, tumour margins, and normal buccal mucosa of patients with oral cancer. Int J Oral Maxillofac Surg. 2018;47(8):976–82.PubMedCrossRef
2.
Curtius K, Wright NA, Graham TA. An evolutionary perspective on field cancerization. Nat Rev Cancer. 2018;18(1):19–32.PubMedCrossRef
3.
Slaughter DP, Southwick HW, Smejkal W. “Field cancerization” in oral stratified squamous epithelium. Clinical implications of multicentric origin. Cancer. 1953;6(5):963–8.PubMedCrossRef
4.
Bosch FX, Ouhayoun J-P, Bader BL, Collin C, Grund C, Lee I, et al. Extensive changes in cytokeratin expression patterns in pathologically affected human gingiva. Virchows Archiv B. 1989;58(1):59.CrossRef
5.
Bongers V, Snow GB, De Vries N, Braakhuis BJ. Potential early markers of carcinogenesis in the mucosa of the head and neck using exfoliative cytology. J Pathol. 1996;178(3):284–9.PubMedCrossRef
6.
Bartkova J, Lukas J, Müller H, Strauss M, Gusterson B, Bartek J. Abnormal patterns of D-type cyclin expression and G1 regulation in human head and neck cancer. Can Res. 1995;55(4):949–56.
7.
Bloching MM, Soulsby H, Naumann A, Aust W, Merkel D, Braun T, et al. Tumor risk assessment by means of immunocytochemical detection of early pre-malignant changes in buccal smears. Oncol Rep. 2008;19(6):1373–9.PubMed
8.
Shin DM, Ro JY, Hong WK, Hittelman WN. Dysregulation of epidermal growth factor receptor expression in premalignant lesions during head and neck tumorigenesis. Can Res. 1994;54(12):3153–9.
9.
Van Oijen M, Rijksen G, Broek Ft, Slootweg PJ. Increased expression of epidermal growth factor receptor in normal epithelium adjacent to head and neck carcinomas independent of tobacco and alcohol abuse. Oral Dis. 1998;4(1):4–8.PubMedCrossRef
10.
Grandis JR, Tweardy DJ. Elevated levels of transforming growth factor α and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Can Res. 1993;53(15):3579–84.
11.
van Oijen MG, Gilsing MMA, Rijksen G, Hordijk GJ, Slootweg PJ. Increased number of proliferating cells in oral epithelium from smokers and ex-smokers. Oral Oncol. 1998;34(4):297–303.PubMedCrossRef
12.
Birchall MA, Schock E, Harmon BV, Gobe G. Apoptosis, mitosis, PCNA and bcl-2 in normal, leukoplakic and malignant epithelia of the human oral cavity: prospective, in vivo study. Oral Oncol. 1997;33(6):419–25.PubMedCrossRef
13.
El-Gazzar R, Macluskey M, Ogden GR. Evidence for a field change effect based on angiogenesis in the oral mucosa? A brief report. Oral Oncol. 2005;41(1):25–30.PubMedCrossRef
14.
Cruz IB, Snijders PJ, Meijer CJ, Braakhuis BJ, Snow GB, Walboomers JM, et al. p53 expression above the basal cell layer in oral mucosa is an early event of malignant transformation and has predictive value for developing oral squamous cell carcinoma. J Pathol. 1998;184(4):360–8.PubMedCrossRef
15.
Lavieille JP, Brambilla E, Riva-Lavieille C, Reyt E, Charachon R, Brambilla C. Immunohistochemical detection of p53 protein in preneoplastic lesions and squamous cell carcinoma of the head and neck. Acta Otolaryngol. 1995;115(2):334–9.PubMedCrossRef
16.
Nakanishi Y, Noguchi M, Mukai K, Matsuno Y, Hirohashi S, Saikawa M, et al. p53 expression in multicentric squamous cell carcinoma and surrounding squamous epithelium of the upper aerodigestive tract. Immunohistochemical analysis of 95 lesions. Cancer. 1995;75(7):1657–62.PubMedCrossRef
17.
Nees M, Homann N, Discher H, Andl T, Enders C, Herold-Mende C, et al. Expression of mutated p53 occurs in tumor-distant epithelia of head and neck cancer patients: a possible molecular basis for the development of multiple tumors. Can Res. 1993;53(18):4189–96.
18.
van Oijen MG, van de Craats JG, Slootweg PJ. p53 overexpression in oral mucosa in relation to smoking. J Pathol. 1999;187(4):469–74.PubMedCrossRef
19.
Waridel F, Estreicher A, Bron L, Flaman JM, Fontolliet C, Monnier P, et al. Field cancerisation and polyclonal p53 mutation in the upper aero-digestive tract. Oncogene. 1997;14(2):163–9.PubMedCrossRef
20.
Van Roy FM, McCrea PD. A role for Kaiso–p120ctn complexes in cancer? Nat Rev Cancer. 2005;5(12):956–64.PubMedCrossRef
21.
Kelly KF, Daniel JM. POZ for effect–POZ-ZF transcription factors in cancer and development. Trends Cell Biol. 2006;16(11):578–87.PubMedCrossRef
22.
Pierre CC, Hercules SM, Yates C, Daniel JM. Dancing from bottoms up–roles of the POZ-ZF transcription factor Kaiso in cancer. Biochim Biophys Acta Rev Cancer. 2019;1871(1):64–74.PubMedCrossRef
23.
Xue X, Zhang J, Lan H, Xu Y, Wang H. Kaiso protects human umbilical vein endothelial cells against apoptosis by differentially regulating the expression of B-cell CLL/lymphoma 2 family members. Sci Rep. 2017;7(1):1–16.
24.
Bassey-Archibong BI, Rayner LG, Hercules SM, Aarts CW, Dvorkin-Gheva A, Bramson JL, et al. Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells. Cell Death Dis. 2017;8(3):e2689.PubMedPubMedCentralCrossRef
25.
Koh D-I, Han D, Ryu H, Choi W-I, Jeon B-N, Kim M-K, et al. KAISO, a critical regulator of p53-mediated transcription of CDKN1A and apoptotic genes. Proc Natl Acad Sci. 2014;111(42):15078–83.PubMedPubMedCentralCrossRef
26.
Vermeulen JF, van de Ven RA, Ercan C, van der Groep P, van der Wall E, Bult P, et al. Nuclear Kaiso expression is associated with high grade and triple-negative invasive breast cancer. PLoS ONE. 2012;7(5):e37864.PubMedPubMedCentralCrossRef
27.
Jones J, Wang H, Karanam B, Theodore S, Dean-Colomb WM, Welch DR, et al. Nuclear localization of Kaiso as a prognostic biomarker and promotion of EMT in infiltrating ductal breast carcinomas. Am Soc Clin Oncol. 2014.
28.
Bassey-Archibong BI, Hercules SM, Rayner LG, Skeete DH, Connell SPS, Brain I, et al. Kaiso is highly expressed in TNBC tissues of women of African ancestry compared to Caucasian women. Cancer Causes Control. 2017;28(11):1295–304.PubMedPubMedCentralCrossRef
29.
Kwiecien JM, Bassey-Archibong BI, Dabrowski W, Rayner LG, Lucas AR, Daniel JM. Loss of Kaiso expression in breast cancer cells prevents intra-vascular invasion in the lung and secondary metastasis. PLoS ONE. 2017;12(9):e0183883.PubMedPubMedCentralCrossRef
30.
Dai S-D, Wang Y, Miao Y, Zhao Y, Zhang Y, Jiang G-Y, et al. Cytoplasmic Kaiso is associated with poor prognosis in non-small cell lung cancer. BMC Cancer. 2009;9(1):1–13.CrossRef
31.
Jones J, Wang H, Zhou J, Hardy S, Turner T, Austin D, et al. Nuclear Kaiso indicates aggressive prostate cancers and promotes migration and invasiveness of prostate cancer cells. Am J Pathol. 2012;181(5):1836–46.PubMedPubMedCentralCrossRef
32.
Wang H, Liu W, Black S, Turner O, Daniel JM, Dean-Colomb W, et al. Kaiso, a transcriptional repressor, promotes cell migration and invasion of prostate cancer cells through regulation of miR-31 expression. Oncotarget. 2016;7(5):5677.PubMedCrossRef
33.
Jones J, Mukherjee A, Karanam B, Davis M, Jaynes J, Reams RR, et al. African Americans with pancreatic ductal adenocarcinoma exhibit gender differences in Kaiso expression. Cancer Lett. 2016;380(2):513–22.PubMedPubMedCentralCrossRef
34.
SeyedJafari SM, Hunger R. IHC optical density score: a new practical method for quantitative immunohistochemistry image analysis. Appl Immunohistochem Mol Morphol. 2017;25(1):e12–3.CrossRef
35.
BRODERS AC. The microscopic grading of cancer. The surgical clinics of north America. 1941;21:947–62.
36.
Bryne M, Koppang HS, Lilleng R, Kjærheim Å. Malignancy grading of the deep invasive margins of oral squamous cell carcinomas has high prognostic value. J Pathol. 1992;166(4):375–81.PubMedCrossRef
37.
Boxberg M, Jesinghaus M, Dorfner C, Mogler C, Drecoll E, Warth A, et al. Tumour budding activity and cell nest size determine patient outcome in oral squamous cell carcinoma: proposal for an adjusted grading system. Histopathology. 2017;70(7):1125–37.PubMedCrossRef
38.
van Houten VM, Tabor MP, van den Brekel MW, Alain Kummer J, Denkers F, Dijkstra J, et al. Mutated p53 as a molecular marker for the diagnosis of head and neck cancer. J Pathol. 2002;198(4):476–86.PubMedCrossRef
39.
El-Naggar AK, Lai S, Luna MA, Zhou X-D, Weber RS, Goepfert H, et al. Sequential p53 mutation analysis of pre-invasive and invasive head and neck squamous carcinoma. Int J Cancer. 1995;64(3):196–201.PubMedCrossRef
40.
Reda E, Reda N. Over expression of p53 and p21 in normal oral mucosa adjacent to resected squamous cell carcinomas. 2005.
41.
Izzo JG, Papadimitrakopoulou VA, Li XQ, Ibarguen H, Lee JS, Ro JY, et al. Dysregulated cyclin D1 expression early in head and neck tumorigenesis: in vivo evidence for an association with subsequent gene amplification. Oncogene. 1998;17(18):2313–22.PubMedCrossRef
42.
Ortiz BH, Ailawadi M, Colitti C, Muto MG, Deavers M, Silva EG, et al. Second primary or recurrence? Comparative patterns of p53 and K-ras mutations suggest that serous borderline ovarian tumors and subsequent serous carcinomas are unrelated tumors. Can Res. 2001;61(19):7264–7.
43.
Werkmeister R, Brandt B, Joos U. The erbB oncogenes as prognostic markers in oral squamous cell carcinomas. Am J Surg. 1996;172(6):681–3.PubMedCrossRef
44.
Szymańska K, Levi JE, Menezes A, Wünsch-Filho V, Eluf-Neto J, Koifman S, et al. TP53 and EGFR mutations in combination with lifestyle risk factors in tumours of the upper aerodigestive tract from South America. Carcinogenesis. 2010;31(6):1054–9.PubMedCrossRef
45.
Astekar M, Joshi A, Ramesh G, Metgud R. Expression of vascular endothelial growth factor and microvessel density in oral tumorigenesis. J Oral Maxillofac Pathol. 2012;16(1):22.PubMedPubMedCentralCrossRef
46.
López-Blanc SA, Collet AM, Gandolfo MS, Femopase F, Hernández SL, Tomasi VH, et al. Nucleolar organizer regions (AgNOR) and subepithelial vascularization as field cancerization markers in oral mucosa biopsies of alcoholic and smoking patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;108(5):747–53.PubMedCrossRef
47.
Daniel: The p120 ctn-binding partner Kaiso is a bi-modal... - Google Scholar [
48.
Buck-Koehntop BA, Stanfield RL, Ekiert DC, Martinez-Yamout MA, Dyson HJ, Wilson IA, et al. Molecular basis for recognition of methylated and specific DNA sequences by the zinc finger protein Kaiso. Proc Natl Acad Sci. 2012;109(38):15229–34.PubMedPubMedCentralCrossRef
49.
Zhenilo S, Deyev I, Litvinova E, Zhigalova N, Kaplun D, Sokolov A, et al. DeSUMOylation switches Kaiso from activator to repressor upon hyperosmotic stress. Cell Death Differ. 2018;25(11):1938–51.PubMedPubMedCentralCrossRef
50.
Cofre J, Menezes JR, Pizzatti L, Abdelhay E. Knock-down of Kaiso induces proliferation and blocks granulocytic differentiation in blast crisis of chronic myeloid leukemia. Cancer Cell Int. 2012;12(1):1–14.CrossRef
51.
Pierre C. Kaiso: a novel mediator of intestinal inflammation and tumorigenesis [PhD Thesis]. 2015.
Metadata
Title
Expressional variations of Kaiso: an association with pathological characteristics and field cancerization of OSCC
Authors
Shaheen Ahmed
Saeed Khan
Muhammad Asif Qureshi
Uzma Bukhari
Mehak Anis
Muhammad Nouman Mughal
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2022
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-022-10014-7

Other articles of this Issue 1/2022

BMC Cancer 1/2022 Go to the issue

Study protocol

Treatment outcomes of esophageal cancer in Eastern Africa: protocol of a multi-center, prospective, observational, open cohort study

Research

Safety and efficacy of irinotecan, oxaliplatin, and capecitabine (XELOXIRI) regimen with or without targeted drugs in patients with metastatic colorectal cancer: a retrospective cohort study

Research article

Local detection of microvessels in IDH-wildtype glioblastoma using relative cerebral blood volume: an imaging marker useful for astrocytoma grade 4 classification

Research

Molecular signatures of tumor progression in pancreatic adenocarcinoma identified by energy metabolism characteristics

Retraction Note

Retraction Note: Identification of novel signaling components in N,N’-Dinitrosopiperazine-mediated metastasis of nasopharyngeal Carcinoma by quantitative phosphoproteomics

Research

A new finding in the key prognosis-related proto-oncogene FYN in hepatocellular carcinoma based on the WGCNA hub-gene screening trategy
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits