Tumor budding - A promising prognostic histopathological parameter in oral squamous cell carcinoma - A comparative immunohistochemical study

Abstract

Introduction: The majority of the head and neck squamous cell carcinomas (HNSCC) occur in the oral cavity. Even with advances in cancer therapy only minor improvements in the survival of HNSCC patients have taken place and approximately 350,000 patients die annually of HNSCC worldwide. Tumor budding (TB) is a novel and promising histo-morphological parameter that has been studied in many cancers. The presence of TB is associated with lymph node and distant metastasis as well as poor survival, independently of the applied scoring system. The depth of tumor invasion (D) measured from the surface of the tumor to the deepest point of invasion is also an important prognostic parameter for oral squamous cell carcinoma (OSCC) with a cutoff point of 4 mm. Both taken together constitute BD model and it has also been found to be an independent prognostic factor for patients with OSCC. Therefore, it would be highly beneficial to evaluate TB and BD model in routine histopathological reporting.

Aims and objectives: This study aims to compare the detection of TB in hematoxylin-eosin and pan-cytokeratin stained immune-histochemical sections of OSCC and also to evaluate whether BD score can serve as a reliable prognostic indicator for OSCC.

Methodology: A total of 30 formalin-fixed, paraffin-embedded tissue blocks of clinically and histopathologically diagnosed cases of OSCC were retrieved. One section was stained with hematoxylin and eosin and the other was processed for pancytokeratin immunohistochemistry to evaluate tumor buds. Depth of invasion (D) was also evaluated to achieve the BD score.

Results: Statistical significance (P < 0.001) was noted between TB score evaluated in hematoxylin and eosin (H&E) and pancytokeratin stained sections. There was no statistical significance between age, gender, site of lesion, clinical staging, survival and BD score.

Conclusion: Immunohistochemical analysis of TB is superior to H&E staining in detection of tumor buds at the tumor invasive front.

Keywords: BD score; depth of invasion; oral squamous cell carcinoma; tumor budding.

Figure 1

(a) Hematoxylin and eosin stained section showing score 2 tumour buds (×10) Inset (×40). (b) Pan cytokeratin stained section showing score 2 tumour buds ((×10) (Inset ×40)

Figure 2

(a) Hematoxylin and eosinstained section showing Score 0 tumour buds (×4) Inset (×10). (b) Pan cytokeratin stained section showing Score 2 tumour buds (×4) (Inset 10)

Figure 3

(a) Hematoxylin and eosinstained section showing BD score 2 (×4). (b) Hematoxylin and eosinstained section showing BD score 1 (×4)

Figure 4

(a) Hematoxylin and eosinstained section showing Type 3 predominant pattern of invasion (×4). (b) Hematoxylin and eosinstained section showing Type 4 predominant pattern of invasion (×4). (c) Hematoxylin and eosinstained section showing Type 5 worst pattern of invasion (×4)

Graph 1

Cox regression analysis for survival of patients with BD score 1 and 2. (B-Tumour Budding and D- Depth of invasion)