Keywords
odontogenic myxoma, immunohistochemistry, tumor markers, angiogenesis.
How to Cite
Immunohistochemical profile of odontogenic myxoma, with a focus on microvascular density and tumor aggressiveness markers. (2020). Odontoestomatología, 22(35), 52-61. https://doi.org/10.22592/ode2020n35a7
Abstract
Immunohistochemistry tests were
performed in 31 samples to elucidate the
biological behavior of the odontogenic
myxoma (OM), using markers related to
mechanisms of tumor progression (adhesion,
angiogenesis, apoptosis, inflammation
and cell proliferation). Odontogenic
epithelium was detected in four samples
with CK19 and CD138; the latter had a
low expression in the extracellular matrix
(ECM) and a high expression in tumor
cells. The mean microvascular density
(MVD), assessed with CD34 and VEGF-A,
was 7.51 and 5.35 blood vessels. A high
expression of orosomucoid-1 and mast cell
tryptase was observed in tumor cells and
ECM, while calretinin was negative. The
immunohistochemical profile mentioned
above, as well as the low expression of Ki-
67, Bcl-2 and p53 and the relatively low
MVD, suggest that the proliferative, antiapoptotic
and angiogenic activities do not
represent the main growing mechanisms
of OM, which could be associated to other
events, such as immunomodulation and
ECM degradation.
References
1. El-Naggar Chan JKC, Grandis JR, Takata T,
Slootweg P, editors. WHO classification of
Head and Neck Tumours. Chapter 8: Odontogenic
and maxilofacial bone tumours. 4th edition,
IARC: Lyon 2017, p.205-260.
2. Mosqueda-Taylor A, Ledesma-Montes C, Caballero-
Sandoval S, Portilla-Robertson J, Ruíz-
Godoy RLM, Meneses-García A. Odontogenic
tumors in México. A collaborative retrospective
study of 349 cases. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod. 1997; 84 (6): 672-
5.
3. Wright JM, Soluk-Tekkesin M. Odontogenic
tumors: where are we in 2017? J Istanb Univ
Fac Dent. 2017; 51 (3 Suppl 1): s10-30.
4. Gonzalez-Galvan MC, Mosqueda-Taylor A,
Bologna-Molina R, Setien-Olarra A, Marichalar-
Mendia X, Aguirre-Urizar JM. Evaluation
of the osteoclastogenic process associated
with RANK / RANK-L / OPG in odontogenic
myxomas. Med Oral Patol Oral Cir Bucal.
2018; 23 (3): e315-9.
5. Kanitkar S, Kamat M, Tamagond S, Vareakr A,
Datar U. Peripheral odontogenic myxoma in
a 12-year-old girl: a rare entity. J Korean Assoc
Oral Maxillofac Sur. 2017;43: 178.81. doi:
10.5125/jkaoms.2017.43.3.178
6. Chrcanovic BR, Gomez RS. Odontogenic
myxoma: an updated analysis of 1,692 cases
reported in the literature. Oral Dis. 2019; 25:
676-83. doi: 10.1111/odi.12875
7. Bologna-Molina R, Mosqueda-Taylor A, Dominguez-
Malagon H, Salazar-Rodriguez S, Tapia
G, Gonzalez-Gonzalez R, Molina-Frechero
N. Immunolocalization of VEGF-A and orosomucoid-
1 in odontogenic myxoma. Rom J
Morphol Embryol. 2015; 56 (2): 465-73.
8. Weidner N, Semple JP, Welch WR, Folkman
J. Tumor angiogenesis and metastasis – correlation
in invasive breast carcinoma. N Engl J
Med. 1991; 32: 1–8.
9. Martínez-Mata G, Mosqueda-Taylor A, Carlos-
Bregni R, Paes de Almeida O, Contreras-
Vidaurre E, Vargas PA, Cano-Valdéz AM,
Domínguez-Malagón H. Odontogenic myxoma:
clinico-pathological, immunohistochemical
and ultrastructural findings of a multicentric
series. Oral Oncol. 2007; 44: 601-7.
doi:10.1016/j.oraloncology 2007.08.009.
10. Lombardi T, Lock C, Samson J, Odell EW.
S100, alpha-smooth muscle actin and cytokeratin19
immunohistochemistry in odontogenic
and soft tissue myxomas. J Clin Pathol. 1995;
48: 759-62.
11. Etemad-Moghadam S, Alaeddinni M. A comparative
study of syndecan-1 expression in
different odontogenic tumors. J Oral Biol
Craniofac Res. 2017; 7: 23-6. doi: 10.1016/j.
jobcr.2016.11.001
12. Bologna-Molina R, Salazar-Rodríguez S,
Bedoya-Borella AM, Carreon-Burciaga RG,
Tapia-Repetto G, Molina-Frechero N. A
histopathological and immunohistochemical
analysis of ameloblastic fibrodentinoma.
Case Rep Pathol. 2013; 2013:604560. doi:
10.1155/2013/604560
13. Bologna-Molina R, Mosqueda-Taylor A, López-
Corella E, Paes de Almeida O, Carrasco-
Daza D, Farfán-Morales JE, Molina-Frechero
N, Damián-Matsumura P. Comparative expression
of syndecan-1 and Ki-67 in peripheral and
desmoplastic ameloblastomas and ameloblastic
carcinoma. Pathol Int. 2009; 59: 229–33.
14. Manne RK, Kumar VS, Venkata Sarath P,
Anumula L, Mundlapudi S, Tanikonda R.
Odontogenic myxoma of the mandible.
Case Rep Dent. 2012; 2012: 214704. doi:
10.1155/2012/214704
15. Alaeddini M, Etemad-Moghadam S, Baghaii F.
Comparative expression of calretinin in selected
odontogenic tumours: a possible relationship
to histogenesis. Histopathology. 2008; 52 (3):
299–304.
16. Terracciano LM, Mhawech P, Suess K,
D’Armiento M, Lehmann FS, Jundt G, Moch
H, Sauter G, Mihatsch MJ. Calretinin as a marker
for cardic myxoma. Diagnostic and histogenetic
considerations. Am J Clin Pathol. 2000;
114 (5): 754-9.
17. Mistry D, Altini M, Coleman HG, Ali H,
Maiorano E. The spatial and temporal expression
of calretinin in developing rat molars
(Rattus norvegicus). Arch Oral Biol. 2001;
46 (10): 973-81.
18. Altini M, Coleman H, Doglioni C, Favia G,
Maiorano E. Calretinin expression in ameloblastomas.
Histopatholohy. 2000; 37 (1): 27-
32.
19. Seifi S, Shafaie S, Ghadiri S. Microvessel density
in follicular cysts, keratocystic odontogenic
tumours and ameloblastomas. Asian Pacific J
Cancer Prev. 2001; 12 (2): 351-56.
20. Treville Pereira, Shashibhushan Dodal, Avinash
Tamgadge, Sudhir Bhalerao, Sandhya Tamgadge.
Quantitative evaluation of microvessel
density using CD34 in clinical variants of ameloblastoma:
An immunohistochemical study.
J Oral Maxillofac Pathol. 2016; 20 (1): 51-8.
Doi: 10.4103/0973-029X.180929
21. Gupta B, Chandra S, Singh A, Sah K, Raj
V, Gupta V. The role of vascular endothelial
growth factor in proliferation of odontogenic
cysts and tumors: An immunohistochemical
study. Dent Res J. 2016; 13 (3): 256-63.
22. García-Muñoz A, Rodríguez MA, Bologna-
Molina R, Cázares-Raga FE, Hernández-Hernández
FC, Farfán-Morales JE, Trujillo JJ, Licéaga-
Escalera C, Mendoza-Hernández G. The
orosomucoid 1 protein (a1 acid glycoprotein) is
overexpressed in odontogenic myxoma. Proteome
Sci. 2012; 10 (1): 49.
23. Irmak S, Oliveira-Ferrer L, Singer BB, Ergun
S, Tilki D. Pro-angiogenic properties of orosomucoid
(ORM). Exp Cell Res. 2009; 315 (18):
3201–09.
24. Ligresti G, Aplin AC, Dunn BE, Morishita A,
Nicosia RF. The acute phase reactant orosomucoid-
1 is a bimodal regulator of angiogenesis
with time- and context dependent inhibitory
and stimulatory properties. Plos One.
2012; 7 (8): e41387. doi: 10.1371/journal.
pone.0041387.
25. Kouhsoltani M, Halimi M, Dibazar S. A positive
correlation between immunohistochemical
expression of CD31 and mast cell tryptase in
odontogenic tumor. Pol J Pathol. 2015; 66 (2):
170-5.
26. Fajardo I, Pejler G. Human mast cell ß-tryptase
is a gelatinase. J Immunol. 2003; 171 (3):
1493-9
27. Huang S, Lu F, Chen Y, Huang B, Liu M. Mast
cell degranulation in human periodontitis. J Periodontol.
2013; 84 (2): 248-55.
28. De Assis Caldas Pereira F, Araújo Silva Gurgel
CA, Ramos EA, Vidal MT, Pinheiro AL, Jurisic
V, Sales CB, Cury PR, dos Santos JN. Distribution
of mast cell in benign odontogenic tumors.
Tumor Biol. 2012; 33 (2): 455-61.
29. Iezzi G, Piatelli A, Rubini C, Artese L, Fiorini
M, Carinci F. MIB-1, Bcl-2 and p53 in odontogenic
myxomas of the jaws. Acta Otorhinolaryngol
Ital. 2007; 27 (5): 237-42.
30. Bast B, Pogrel MA, Regezi JA. The expression of
apoptotic proteins and matrix metalloproteinases
in odontogenic myxomas. J Oral Maxillofac
Surg. 2003; 61 (12): 1463-6.
Slootweg P, editors. WHO classification of
Head and Neck Tumours. Chapter 8: Odontogenic
and maxilofacial bone tumours. 4th edition,
IARC: Lyon 2017, p.205-260.
2. Mosqueda-Taylor A, Ledesma-Montes C, Caballero-
Sandoval S, Portilla-Robertson J, Ruíz-
Godoy RLM, Meneses-García A. Odontogenic
tumors in México. A collaborative retrospective
study of 349 cases. Oral Surg Oral Med Oral
Pathol Oral Radiol Endod. 1997; 84 (6): 672-
5.
3. Wright JM, Soluk-Tekkesin M. Odontogenic
tumors: where are we in 2017? J Istanb Univ
Fac Dent. 2017; 51 (3 Suppl 1): s10-30.
4. Gonzalez-Galvan MC, Mosqueda-Taylor A,
Bologna-Molina R, Setien-Olarra A, Marichalar-
Mendia X, Aguirre-Urizar JM. Evaluation
of the osteoclastogenic process associated
with RANK / RANK-L / OPG in odontogenic
myxomas. Med Oral Patol Oral Cir Bucal.
2018; 23 (3): e315-9.
5. Kanitkar S, Kamat M, Tamagond S, Vareakr A,
Datar U. Peripheral odontogenic myxoma in
a 12-year-old girl: a rare entity. J Korean Assoc
Oral Maxillofac Sur. 2017;43: 178.81. doi:
10.5125/jkaoms.2017.43.3.178
6. Chrcanovic BR, Gomez RS. Odontogenic
myxoma: an updated analysis of 1,692 cases
reported in the literature. Oral Dis. 2019; 25:
676-83. doi: 10.1111/odi.12875
7. Bologna-Molina R, Mosqueda-Taylor A, Dominguez-
Malagon H, Salazar-Rodriguez S, Tapia
G, Gonzalez-Gonzalez R, Molina-Frechero
N. Immunolocalization of VEGF-A and orosomucoid-
1 in odontogenic myxoma. Rom J
Morphol Embryol. 2015; 56 (2): 465-73.
8. Weidner N, Semple JP, Welch WR, Folkman
J. Tumor angiogenesis and metastasis – correlation
in invasive breast carcinoma. N Engl J
Med. 1991; 32: 1–8.
9. Martínez-Mata G, Mosqueda-Taylor A, Carlos-
Bregni R, Paes de Almeida O, Contreras-
Vidaurre E, Vargas PA, Cano-Valdéz AM,
Domínguez-Malagón H. Odontogenic myxoma:
clinico-pathological, immunohistochemical
and ultrastructural findings of a multicentric
series. Oral Oncol. 2007; 44: 601-7.
doi:10.1016/j.oraloncology 2007.08.009.
10. Lombardi T, Lock C, Samson J, Odell EW.
S100, alpha-smooth muscle actin and cytokeratin19
immunohistochemistry in odontogenic
and soft tissue myxomas. J Clin Pathol. 1995;
48: 759-62.
11. Etemad-Moghadam S, Alaeddinni M. A comparative
study of syndecan-1 expression in
different odontogenic tumors. J Oral Biol
Craniofac Res. 2017; 7: 23-6. doi: 10.1016/j.
jobcr.2016.11.001
12. Bologna-Molina R, Salazar-Rodríguez S,
Bedoya-Borella AM, Carreon-Burciaga RG,
Tapia-Repetto G, Molina-Frechero N. A
histopathological and immunohistochemical
analysis of ameloblastic fibrodentinoma.
Case Rep Pathol. 2013; 2013:604560. doi:
10.1155/2013/604560
13. Bologna-Molina R, Mosqueda-Taylor A, López-
Corella E, Paes de Almeida O, Carrasco-
Daza D, Farfán-Morales JE, Molina-Frechero
N, Damián-Matsumura P. Comparative expression
of syndecan-1 and Ki-67 in peripheral and
desmoplastic ameloblastomas and ameloblastic
carcinoma. Pathol Int. 2009; 59: 229–33.
14. Manne RK, Kumar VS, Venkata Sarath P,
Anumula L, Mundlapudi S, Tanikonda R.
Odontogenic myxoma of the mandible.
Case Rep Dent. 2012; 2012: 214704. doi:
10.1155/2012/214704
15. Alaeddini M, Etemad-Moghadam S, Baghaii F.
Comparative expression of calretinin in selected
odontogenic tumours: a possible relationship
to histogenesis. Histopathology. 2008; 52 (3):
299–304.
16. Terracciano LM, Mhawech P, Suess K,
D’Armiento M, Lehmann FS, Jundt G, Moch
H, Sauter G, Mihatsch MJ. Calretinin as a marker
for cardic myxoma. Diagnostic and histogenetic
considerations. Am J Clin Pathol. 2000;
114 (5): 754-9.
17. Mistry D, Altini M, Coleman HG, Ali H,
Maiorano E. The spatial and temporal expression
of calretinin in developing rat molars
(Rattus norvegicus). Arch Oral Biol. 2001;
46 (10): 973-81.
18. Altini M, Coleman H, Doglioni C, Favia G,
Maiorano E. Calretinin expression in ameloblastomas.
Histopatholohy. 2000; 37 (1): 27-
32.
19. Seifi S, Shafaie S, Ghadiri S. Microvessel density
in follicular cysts, keratocystic odontogenic
tumours and ameloblastomas. Asian Pacific J
Cancer Prev. 2001; 12 (2): 351-56.
20. Treville Pereira, Shashibhushan Dodal, Avinash
Tamgadge, Sudhir Bhalerao, Sandhya Tamgadge.
Quantitative evaluation of microvessel
density using CD34 in clinical variants of ameloblastoma:
An immunohistochemical study.
J Oral Maxillofac Pathol. 2016; 20 (1): 51-8.
Doi: 10.4103/0973-029X.180929
21. Gupta B, Chandra S, Singh A, Sah K, Raj
V, Gupta V. The role of vascular endothelial
growth factor in proliferation of odontogenic
cysts and tumors: An immunohistochemical
study. Dent Res J. 2016; 13 (3): 256-63.
22. García-Muñoz A, Rodríguez MA, Bologna-
Molina R, Cázares-Raga FE, Hernández-Hernández
FC, Farfán-Morales JE, Trujillo JJ, Licéaga-
Escalera C, Mendoza-Hernández G. The
orosomucoid 1 protein (a1 acid glycoprotein) is
overexpressed in odontogenic myxoma. Proteome
Sci. 2012; 10 (1): 49.
23. Irmak S, Oliveira-Ferrer L, Singer BB, Ergun
S, Tilki D. Pro-angiogenic properties of orosomucoid
(ORM). Exp Cell Res. 2009; 315 (18):
3201–09.
24. Ligresti G, Aplin AC, Dunn BE, Morishita A,
Nicosia RF. The acute phase reactant orosomucoid-
1 is a bimodal regulator of angiogenesis
with time- and context dependent inhibitory
and stimulatory properties. Plos One.
2012; 7 (8): e41387. doi: 10.1371/journal.
pone.0041387.
25. Kouhsoltani M, Halimi M, Dibazar S. A positive
correlation between immunohistochemical
expression of CD31 and mast cell tryptase in
odontogenic tumor. Pol J Pathol. 2015; 66 (2):
170-5.
26. Fajardo I, Pejler G. Human mast cell ß-tryptase
is a gelatinase. J Immunol. 2003; 171 (3):
1493-9
27. Huang S, Lu F, Chen Y, Huang B, Liu M. Mast
cell degranulation in human periodontitis. J Periodontol.
2013; 84 (2): 248-55.
28. De Assis Caldas Pereira F, Araújo Silva Gurgel
CA, Ramos EA, Vidal MT, Pinheiro AL, Jurisic
V, Sales CB, Cury PR, dos Santos JN. Distribution
of mast cell in benign odontogenic tumors.
Tumor Biol. 2012; 33 (2): 455-61.
29. Iezzi G, Piatelli A, Rubini C, Artese L, Fiorini
M, Carinci F. MIB-1, Bcl-2 and p53 in odontogenic
myxomas of the jaws. Acta Otorhinolaryngol
Ital. 2007; 27 (5): 237-42.
30. Bast B, Pogrel MA, Regezi JA. The expression of
apoptotic proteins and matrix metalloproteinases
in odontogenic myxomas. J Oral Maxillofac
Surg. 2003; 61 (12): 1463-6.