Diagnostic and prognostic role of protein and ultrastructural alterations at cell–extracellular matrix junctions in neoplastic progression of human oral malignancy

ABSTRACT

Despite advancements in technology and increase in favorable outcomes associated with oral cancer, early detection remains the most significant factor in limiting mortality. The current study aimed to develop early diagnostic and prognostic markers for oral tumorigenesis. Protein and ultrastructural alterations at cell-extracellular matrix (ECM) adhesion junctions were examined concurrently using immunohistochemistry (IHC) and transmission electron microscopy (TEM) on progressive grade of oral carcinomas (n = 285). The expression of hemidesmosome (HD) proteins-integrin β4, BP180, and laminin-5 increased in hyperplasia as compared to normal, and significantly increased further, as the disease progressed. TEM analysis in parallel tissues revealed a significant decrease in HD number and increase in the length of basal lamina (BL) in hyperplasia. With cancer progression, the severity of ultrastructural alterations increased gradually and significantly. Overexpression of HD proteins, decrease in HD number and increase in BL length significantly correlated with nodal metastasis, local recurrence, and recurrence-free survival of patients. Concurrent use of IHC and TEM can add value to early recognition of neoplastic changes in primary carcinomas of oral cavity. In this regard, altered expression of integrin β4 and laminin-5, loss of HDs, and increased BL length could offer criteria for early diagnosis and prognosis of oral malignancy.

KEYWORDS:

• Oral precancer
• oral squamous cell carcinoma
• transmission electron microscopy
• hemidesmosomes
• basal lamina

Author contributions

Harsh Dongre: Conceptualization, Methodology, Formal analysis, Investigation, Writing- Original draft; Snehal Mahadik: Methodology, Formal analysis, Investigation; Chetan Ahire: Methodology, Formal analysis, Investigation; Shilpi Sharma: Resources and Data curation; Fatima Lukmani: Investigation and resources; Pallavi Rane: Statistical analysis and data curation; Asawari Patil: Investigation and resources; Devendra Chaukar: Patients selection, Data curation and project administration; Sudeep Gupta: Project administration and supervision; Sharada Sawant: Conceptualization, Methodology, Formal analysis, Writing, reviewing and final approval of manuscript, Supervision, Project administration and funding acquisition

Acknowledgments

The authors would like to acknowledge the electron microscopy (EM) and digital imaging facilities of Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Navi Mumbai, India. Authors would also like to thank Mrs. Siddhi Redkar and Mr. Shridhar Nadkar for their contribution in TEM protocol at EM facility, ACTREC. The authors thank Ms. Snigdha Gauniyal, professional English language editor, Kalyan, Mumbai, for editing manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/01913123.2022.2114565

Additional information

Funding

This work was supported by the Advanced Centre for Treatment, Research & Education in Cancer, Tata Memorial Centre under the intramural grant (number 3335; Advanced Centre for Treatment, Research and Education in CancerAdvanced Centre for Treatment, Research and Education in Cancer [3335];