Impact of Immunohistochemical Expression of Collagen III and MMP-14 in Odontogenic Keratocyst


  • Helin F. Hassan Oral Diagnosis Department, College of Dentistry, University of Sulaimani, Kurdistan Region, Iraq. Author
  • Balkis T. Garib Oral Diagnosis Department, College of Dentistry, University of Sulaimani, Kurdistan Region, Iraq. Author
  • Dena N. Mohammad Oral Diagnosis Department, College of Dentistry, University of Sulaimani, Kurdistan Region, Iraq. Author



Immunohistochemical, Keratocyst, MMP14, Collagen III, Sulaimani


Objective: Immunohistochemical expression of collagen III and MMP14 was evaluated in odontogenic keratocyst, and correlated to
the clinicopathological parameters to remark on the role of these markers in the biological behavior of the cyst.

Twenty-three odontogenic keratocysts samples were collected from three pathological laboratories in Sulaimani.
Demographic information and the available radiographic investigation were recorded. The immune expression of collagen III and
MMP14 was evaluated and related to the clinicopathological variables. Chi-square test was used for analysis and a p-value of 0.05 was
cut off point for significance.

Males were predominantly affected by odontogenic keratocysts lesions (69.6%), which were mainly detected in the >35 years
age groups. Keratocyst lesions were seen more frequently in the mandible (82.6%), with well-defined borders, and unilocular
appearance. Collagen III was oriented more commonly in a parallel direction (70.8%), with moderate intensity (45.8%). MMP14
revealed cytoplasmic expression in the epithelial lining of the keratocyst (100%), score 3 was the most prevalent expression (54.2%)
in the cystic wall, and prominent inflammation and epithelial separation were detected with high scoring of MMP14, which were
(57.1%) and (56.3%) respectively.

Both markers had independent combined roles in the cyst’s biological behavior, including the prevalent parallel direction of the collagen III, while overexpression of the MMP14 might have an impact role in the aggressive behavior of the lesion.


Menon S. Keratocystic odontogenic tumours:

etiology, pathogenesis and treatment revisited. J

Maxillofac Oral Surg. 2015;14(3):541-7.

Qu J, Yu F, Hong Y, Guo Y, Sun L, Li X, et al.

Underestimated PTCH1 mutation rate in sporadic

keratocystic odontogenic tumors. Oral Oncol.


The International Agency for Research on Cancer.

Pathology and Genetics of Head and Neck

Tumours [OP]

(Medicine):9789283224174:Medicine & Health

Science [email protected]. World Health

Organization. 2005. p. 430.

EI-Naggar AK, Chan JKC, Grandis JR, Takata

TSP. WHO Classification of Head and Neck

Tumours. WHO classification of Head and neck

Tumors 2017. 2017.p 215-220.

Krishna R, Johny J, Punathil S, and Khan NM. A

rare case of odontogenic keratocyst crossing lower

midline. Austin J Dent. 2019;6(1):11-25.

Oral and Maxillofacial Pathology - Brad W.

Neville, DDS, Douglas D. Damm, DDS, Carl M.

Allen, DDS, MSD, Angela C. Chi, DMD - Google


Bhagawati BT, Gupta M, Narang G, Bhagawati S.

Keratocystic odontogenic tumor with an ectopic

tooth in maxilla. Case Rep Dent. 2013;2013:1-4.

Kumari K, Ghosh S, Patil S, Augustine D,

Samudrala Venkatesiah S, Rao RS. Expression of

type III collagen correlates with poor prognosis in

oral squamous cell carcinoma. J Investig Clin

Dent. 2017;8(4):1-7.

D’hondt S, Guillemyn B, Syx D, Symoens S, De

Rycke R, Vanhoutte L, et al. Type III collagen

affects dermal and vascular collagen

fibrillogenesis and tissue integrity in a mutant

Col3a1 transgenic mouse model. Matrix Biol.


Nielsen MJ, Karsdal MA. Type III Collagen.

Biochemistry of Collagens, Laminins and Elastin:

Structure, Function and Biomarkers. Elsevier Inc.;

p 21–30.

Kumari K, Ghosh S, Patil S, Augustine D,

Samudrala Venkatesiah S, Rao RS. Expression of

type III collagen correlates with poor prognosis in

oral squamous cell carcinoma. J Investig Clin

Dent. 2017;8(4):1-7.

Claesson-Welsh L. How the matrix

metalloproteinase MMP14 contributes to the

progression of colorectal cancer. J Clin Invest.


Linklater E, Jewett CE, Prekeris R. Polarized

membrane trafficking in development and disease:

from epithelia polarization to cancer cell invasion.

Cell Polarity Dev Dis. 2018;121-46.

Gobin E, Bagwell K, Wagner J, Mysona D,

Sandirasegarane S, Smith N, et al. A pan-cancer

perspective of matrix metalloproteases (MMP)

gene expression profile and their

diagnostic/prognostic potential. BMC Cancer.


Karande AM, Khandeparkar R, Vergeese CS JH.

Role of molecular markers in understanding the

tumor invasioness of ameloblastoma. Med Res

Chronicles. 2017;4(1):1-9.

Singh H, Shetty DC, Wadhwan V, Aggarwal P. A

quantitative and qualitative comparative analysis

of collagen fibers to determine the role of

connective tissue stroma on biological behavior of

odontogenic. Natl J Maxillofac Surg.


Paulo P, Santos A, Francisco C, Nonaka W, Carlos

·, Galvão Barboza A, et al. Immunohistochemical

analysis of MMP-13 and EMMPRIN in epithelial

odontogenic lesions. Eur Arch Oto-Rhino-

Laryngology. 2019;1(3):3203-11.

Waheed SA, Zaidan TF, Abdullah BH.

Odontogenic cysts and tumors of maxilla and

maxillary sinus (A clinicopathological analysis). J

Baghdad Coll Dent. 2021;33(4):38-43.

Akhtar F, Gillani SM. Clinicopathological

Analysis of Odontogenic Cysts in Iraqi Population.

J Med Chem Sci. 2022;6(4):61-5.

Hosgor H, Tokuc B, Kan B, Coskunses FM.

Evaluation of biopsies of oral and maxillofacial

lesions: A retrospective study. J Korean Assoc

Oral Maxillofac Surg. 2019;45(6):316-23.

Mohanty S, Dabas J, Verma A, Gupta S, Urs AB,

Hemavathy S. Surgical management of the

odontogenic keratocyst: A 20-year experience. Int

J Oral Maxillofac Surg. 2021;50(9):1168-76.

Al-Rawi NH, Al-Siraj AK, Majeed AH.

Comparison of osteoclastogenesis and local

invasiveness of ameloblastoma and keratocystic

odontogenic tumor. Eur J Dent. 2018;12(1):36-42.

Jung HD, Lim JH, Kim HJ, Nam W CI, Jung HD,

Lim JH, et al. Appropriate follow-up period for

odontogenic keratocyst: a retrospective study.

Maxillofac Plast Reconstr Surg. 2021;43(1):1-6.

Karaca Ç, Dere KA, Er N, Aktaş A, Tosun E,

Köseoğlu OT, et al. Recurrence rate of

odontogenic keratocyst treated by enucleation and

peripheral ostectomy retrospective case series with

up to 12 years of follow-up. Med Oral Patol Oral y

Cir Bucal. 2018;23(4):e443-8.

Malaguez GG, Munhoz EA, Rivero ERC, Rados P

V., Oliveira MG. Podoplanin expression in

odontogenic keratocysts associated or not

associated with nevoid Basal cell carcinoma

syndrome. Appl Immunohistochem Mol Morphol.


Shoaee S, Khazaei P, Mashhadiabbas F, Varshosaz

M, Sharifi F, Hessari H. Association between tooth

impaction and odontogenic lesions: A matched

case-control study. Med J Islam Repub Iran.


Kitisubkanchana J, Reduwan NH, Poomsawat S,

Pornprasertsuk-Damrongsri S,

Wongchuensoontorn C. Odontogenic keratocyst

and ameloblastoma: radiographic evaluation. Oral

Radiol 2020 371. 2020;37(1):55-65.

Sánchez-Burgos R, González-Martín-Moro J,

Pérez-Fernández E, Burgueño-García M. Clinical,

radiological and therapeutic features of

keratocystic odontogenic tumours: A study over a

decade. J Clin Exp Dent. 2014;6(3):259-64.

Jahagirdar DS. Role of Thickness of Collagen

Fibers in Odontogenic Keratocyst and Dentigerous

Cyst– A Picrosirius Red Polarized Microscopic

Study. J Med Sci Clin Res. 2017;05(09):28322-7.

Manthapuri S, Sanjeevareddygari S, Mantha H,

Oruganti R V, Reddy S, Vamshi VR. Evaluation of

biological behavior of odontogenic keratocyst and

orthokeratinized odontogenic cyst using

picrosirius red stain: A clinicopathological

retrospective study. J Dr NTR Univ Heal Sci.


Raj Y, Sekhar MSM, Shylaja S, Bhavani SN,

Ramanand OV, Patha S, et al. Evaluation of the

nature of collagen fibers in KCOT, dentigerous

cyst and ameloblastoma using picrosirius red

stain–A comparative study. J Clin Diagnostic Res.

;9(11):ZC0 1-4.

Aggarwal P, Saxena S. Stromal differences in

odontogenic cysts of a common histopathogenesis

but with different biological behavior: A study

with picrosirius red and polarizing microscopy.

Indian J Cancer. 2011;48(2):211-5.

Moure SP, Carrard VC, Lauxen IS, Manso PPA,

Oliveira MG, Martins MD, et al. Collagen and

Elastic Fibers in Odontogenic Entities: Analysis

Using Light and Confocal Laser Microscopic

Methods. Open Dent J. 2011;5(1):116.

Amm HM, Casimir MD, Clark DB, Sohn P MM.

Matrix metalloproteinase expression in

keratocystic odontogenic tumors and primary

cells. Connect Tissue Res. 2014;55(1):97-101.

Ribeiro Ribeiro AL, da Costa NMM, de Siqueira

AS, Brasil da Silva W, da Silva Kataoka MS,

Jaeger RG, et al. Keratocystic odontogenic tumor

overexpresses invadopodia-related proteins,

suggesting invadopodia formation. Oral Surg Oral

Med Oral Pathol Oral Radiol. 2016;122(4):500-8.

Chen KHE, Chen C, Lopez T, Radecki KC,

Bustamante K, Lorenson MY, et al. Use of a novel

camelid-inspired human antibody demonstrates

the importance of MMP-14 to cancer stem cell

function in the metastatic process. Oncotarget.


Lund DK, Mouly V, Cornelison DDW. MMP-14

is necessary but not sufficient for invasion of three-

dimensional collagen by human muscle satellite Cell Physiol.


Fuchigami T, Ono Y, Kishida S, Nakamura N.

Molecular biological findings of ameloblastoma.

Jpn Dent Sci Rev. 2021;57(1):27-32.

Zhang B, Zhang J, Huang HZ, Xu ZY, Xie HL.

Expression and role of metalloproteinase-2 and

endogenous tissue regulator in ameloblastoma. J

Oral Pathol Med. 2010;39(3):219-22.

Kumamoto H, Ooya K. Immunohistochemical

detection of MT1-MMP, RECK, and EMMPRIN

in ameloblastic tumors. J Oral Pathol Med.




How to Cite

Impact of Immunohistochemical Expression of Collagen III and MMP-14 in Odontogenic Keratocyst. (2023). Sulaimani Dental Journal, 10(2), 9.