Objective
Extranodal extension (ENE) is an important prognostic factor in oral squamous cell
carcinoma (OSCC). However, ENE is only confirmed postoperatively by histologic assessment
of the lymph nodes after neck dissection. Accurate identification of ENE preoperatively
would help in management of OSCC.
Study Design
We determined the expression of molecular markers gamma glutamyl hydrolase (GGH),
cyclin-dependent kinase inhibitor-3 (CDKN3), and chromobox homolog-7 (CBX7) using
immunohistochemistry in OSCC clinical samples (n = 35). The intensity of staining was scored using a semiquantitative index (HSCORE).
The association between clinicopathologic parameters and expression of molecular markers
with ENE status was analyzed using chi-square test.
Results
The number of positive nodes and the highest anatomic level of nodal involvement significantly
correlated with ENE (P < .05). High GGH expression was significantly associated with ENE (P < .05), with an increased risk for ENE (odds ratio [OR] 9.9, 95% CI 1.08-91.47, P = .04), whereas no significant association was seen for CDKN3 and CBX7 expression
with ENE. However, a trend toward significance was observed with a high level of CDKN3
and a low level of CBX7 expression with ENE.
Conclusions
Gamma glutamyl hydrolase offers potential as a predictor for ENE in OSCC, whereas
the role of CDKN3 and CBX7 need to be validated in a larger sample.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Oral Surgery, Oral Medicine, Oral Pathology and Oral RadiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Living with oral cancer: epidemiology with particular reference to prevalence and life-style changes that influence survival.Oral Oncol. 2010; 46: 407-410
- Epidemiology of oral cancer in Asia in the past decade–an update (2000-2012).Asian Pac J Cancer Prev. 2013; 14: 5567-5577
- Survival following primary surgery for oral cancer.Oral Oncol. 2009; 5: 201-211
- Extracapsular spread in head and neck squamous cell carcinoma: a systematic review and meta-analysis.Oral Oncol. 2016; 62: 60-71
- Head and Neck cancers—major changes in the American Joint Committee on cancer eighth edition cancer staging manual.CA Cancer J Clin. 2017; 67: 122-137
- Oral squamous cell carcinoma with microscopic extracapsular spread in the cervical lymph nodes.Int J Oral Maxillofac Surg. 2014; 43: 387-392
- Assessment criteria and clinical implications of extranodal extension in head and neck cancer.Am Soc Clin Oncol Educ Book. 2021; 41: 265-278
- An eleven gene molecular signature for extra-capsular spread in oral squamous cell carcinoma serves as a prognosticator of outcome in patients without nodal metastases.Oral Oncol. 2015; 51: 355-362
- Sensitivity and specificity of computed tomography for detection of extranodal spread from metastatic head and neck squamous cell carcinoma.J Laryngol Otol. 2009; 123: 778-782
- Squamous cell carcinoma of the upper aerodigestive tract: the prevalence of microscopic extracapsular spread and soft tissue deposits in the clinically N0 neck.Head Neck. 2002; 24: 258-261
- Expression of matrix metalloproteinase-12 is correlated with extracapsular spread of tumor from nodes with metastasis in head and neck squamous cell carcinoma (2013).Eur Arch Otorhinolaryngol. 2013; 270: 1137-1142
- Correlation between podoplanin expression and extracapsular spread in squamous cell carcinoma of the oral cavity using subjective immunoreactivity scores and semiquantitative image analysis.Head Neck. 2017; 39: 98-108
- Epidermal growth factor receptor gene copy number aberration at the primary tumour is significantly associated with extracapsular spread in oral cancer (2011).Br J Cancer. 2011; 104: 850-855
- Cervical lymph node metastasis in oral cancer: the importance of even microscopic extracapsular spread (2003).Oral Oncol. 2003; 39: 130-137
- Prognostic significance of extracapsular spread of lymph node metastasis from oral squamous cell carcinoma in the clinically negative neck.Int J Oral Maxillofac Surg. 2017; 46: 669-675
- Lymph node metastasis: a bearing on prognosis in squamous cell carcinoma.Indian J Cancer. 2015; 52: 417-424
- High levels of γ-glutamyl hydrolase (GGH) are associated with poor prognosis and unfavorable clinical outcomes in invasive breast cancer (2013).BMC Cancer. 2013; 13: 47
- Characterization of the human gamma-glutamyl hydrolase promoter and its gene expression in human tissues and cancer cell lines.Gene. 2003; 312: 281-288
- Epigenetic regulation of human gamma-glutamyl hydrolase activity in acute lymphoblastic leukemia cells.Am J Hum Genet. 2006; 79: 264-274
- Genoproteomic mining of urothelial cancer suggests {gamma}-glutamyl hydrolase and diazepam-binding inhibitor as putative urinary markers of outcome after chemotherapy.Am J Pathol. 2009; 175: 1824-1830
- Overexpression of kinase-associated phosphatase (KAP) in breast and prostate cancer and inhibition of the transformed phenotype by antisense KAP expression.Mol Cell Biol. 2000; 20: 1723-1732
- CDKN3 is an independent prognostic factor and promotes ovarian carcinoma cell proliferation in ovarian cancer.Oncol Rep. 2014; 31: 1825-1831
- Identifying CDKN3 gene expression as a prognostic biomarker in lung adenocarcinoma via meta-analysis.Cancer Inform. 2015; 14: 183-191
- The tumor suppressor CDKN3 controls mitosis.J Cell Biol. 2013; 201: 997-1012
- Loss of the CBX7 protein expression correlates with a more aggressive phenotype in pancreatic cancer.Eur J Cancer. 2010; 46: 1438-1444
- Loss of the CBX7 gene expression correlates with a highly malignant phenotype in thyroid cancer.Cancer Res. 2008; 68: 6770-6778
- The loss of the CBX7 gene expression represents an adverse prognostic marker for survival of colon carcinoma patients.Eur J Cancer. 2010; 46: 2304-2313
- Role of the chromobox protein CBX7 in lymphomagenesis.Proc Natl Acad Sci U S A. 2007; 104: 5389-5394
- Oncogenic role of the chromobox protein CBX7 in gastric cancer (2010).J Exp Clin Cancer Res. 2010; 29: 114
Zhu W, Zeng N and Wang N. Sensitivity, specificity, accuracy, associated confidence interval and ROC analysis with practical SAS implementations. NESUG Proceedings: Health Care and Life Sciences, Baltimore, Maryland. Available at: https://lexjansen.com/nesug/nesug10/hl/hl07.pdf
Article info
Publication history
Published online: August 11, 2022
Accepted:
July 23,
2022
Received in revised form:
June 21,
2022
Received:
December 5,
2021
Identification
Copyright
© 2022 Elsevier Inc. All rights reserved.