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. 2020 Dec 3;10(12):325.
doi: 10.3390/life10120325.

Any Role of PIK3CA and PTEN Biomarkers in the Prognosis in Oral Squamous Cell Carcinoma?

Anna Starzyńska  1 , Paulina Adamska  1 , Aleksandra Sejda  2 , Monika Sakowicz-Burkiewicz  3 , Łukasz Jan Adamski  1 , Giulia Marvaso  4   5 , Piotr Wychowański  6 , Barbara Alicja Jereczek-Fossa  4   5
Affiliations

Any Role of PIK3CA and PTEN Biomarkers in the Prognosis in Oral Squamous Cell Carcinoma?

Anna Starzyńska et al. Life (Basel). .

Abstract

Oral squamous cell carcinoma (OSCC) accounts for 95% of the lesions in the oral cavity. Despite development in OSCC management, the outcome is still unsatisfactory. Identification of new therapies in OSCC is urgently needed. One objective of such treatment may be a signaling pathway of phosphatidylinositol 3-kinase. The study group included 92 patients treated for OSCC at the University Clinical Centre in Gdańsk, Poland. Study was performed on formalin-fixed paraffin-embedded samples from primary OSCC. Phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) and phosphatase and tensin homolog encoded on chromosome 10 (PTEN) protein expression was assessed by immunohistochemistry (IHC). PIK3CA gene copy number was analyzed using chromogenic and silver in situ hybridization where molecular probes are marked by chromogens and silver ions. PIK3CA IHC H-score ≥ 70 was found in 51.65% patients, and loss of PTEN protein was noticed in 31.46% cases. PIK3CA amplification was detected in 5 tumors. In the case of PTEN protein expression, there was an inverse correlation with the T stage of the primary tumor (r = -0.243) and positive correlation with a 5-year survival (r = 0.235). The number of copies of the PIK3CA gene was associated with the tumor grading (r = 0.208). The present study shows that loss of PTEN protein and the grading (p = 0.040), distant metastases (p = 0.033), smoking (p = 0.016), and alcohol abuse (p = 0.042) were prognostic factors for the survival of patients with OSCC. In contrast, the presence of amplification and OSCC on the floor of the mouth resulted in a nearly six-fold increase in the risk of shortening survival (p = 0.037). Our finding suggests a potential prognostic significance of PTEN loss and PIK3CA amplification in OSCC. Future studies are needed to confirm our results.

Keywords: PIK3CA amplification; PTEN loss; oral squamous cell carcinoma; phosphatidylinositol 3-kinase pathway.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overall survival probability curve according to: (a) PIK3CA protein expression as continuous variable; (b) PIK3CA—H-score using 70 as cut-off point; (c) loss of PTEN; (d) PIK3CA copy number as continuous variable; (e) PIK3CA amplification.
Figure 2
Figure 2
The level of PIK3CA protein in oral squamous cell carcinoma (OSCC) (magnification ×40) (a) H-score = 0, (b) H-score = 70, (c) H-score = 200.
Figure 2
Figure 2
The level of PIK3CA protein in oral squamous cell carcinoma (OSCC) (magnification ×40) (a) H-score = 0, (b) H-score = 70, (c) H-score = 200.
Figure 3
Figure 3
The status of PTEN protein in OSCC (magnification ×40) (a) loss of PTEN, (b) positive PTEN expression.
Figure 3
Figure 3
The status of PTEN protein in OSCC (magnification ×40) (a) loss of PTEN, (b) positive PTEN expression.
Figure 4
Figure 4
Representative examples of chromogenic in situ hybridization/silver in situ hybridization (CISH/SISH) analysis (x40). Black signals: PIK3CA, red signals: chromosome 3 centromere; (a) no amplification PIK3CA/CEP3 < 2, (b) amplification PIK3CA/CEP3 ≥ 2.
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