PhD Scientific Days 2024

Pathological and Oncological Sciences III.

mTOR pathway hyperactivation in POU2F3-positive primary and brain metastatic small cell lung carcinoma

Előadó neve

Dr. Krencz, Ildikó

Előadó munkahelye

Department of Pathology and Experimental Cancer Research, Semmelweis University

Előadó e-mail címe

krencz.ildiko@semmelweis.hu

Az előadás címe

mTOR pathway hyperactivation in POU2F3-positive primary and brain metastatic small cell lung carcinoma

Szerző(k) neve és munkahelye

Ildikó Krencz¹, Dániel Sztankovics¹, Fatime Szalai¹, Dorottya Moldvai¹, Anna Sebestyén¹, Judit Pápay¹

1: Department of Pathology and Experimental Cancer Research, Semmelweis University

Bemutatás módja

Szóbeli

Szekció

Pathological and Oncological Sciences III.

Language of the presentation

English

Preferred session

Pathological and Oncological Sciences

Összefoglaló szövege

POU2F3-positive SCLCs represent about 10% of all SCLCs and are characterised by distinct biological features and cell origin. Despite the high frequency of mTOR pathway alterations in SCLC, there is no clear evidence of subtype dependency of mTOR pathway activation.
The expression of POU2F3, phospho-mTOR (active form of the mTOR kinase), phospho-S6 (downstream target of mTORC1), Rictor (scaffold protein of mTORC2), and phospho-Akt (downstream target of mTORC2) was analysed by immunohistochemistry in 50 primary and 50 brain metastatic SCLCs. The H-score method was used to assess the immunoreactions. A case with a POU2F3 H-score higher than 50 was considered POU2F3-positive.
The prevalence of POU2F3 positivity was 12% in the primary SCLCs and 6% in the brain metastatic SCLCs. In the primary tumours, POU2F3 expression showed a significant positive correlation with the expression of phospho-mTOR (R=0.443, p=0.001) and Rictor (R=0.418, p=0.003). The expression of all the studied mTOR pathway markers were higher in the POU2F3-positive cases. Despite the lower number of POU2F3-positive tumours, similar results were observed in the brain metastases: POU2F3 expression showed a significant positive correlation with the expression of phospho-mTOR (R=0.547, p<0.001), phospho-S6 (R=0.490, p<0.001), and phospho-Akt (R=0.292, p=0.040), and the expression of the mTOR pathway markers was also higher in the POU2F3-positive brain metastases.
Accumulating evidence suggests that each subtype of SCLC has specific therapeutic vulnerabilities. Based on our results, POU2F3-positive SCLCs are characterised by hyperactivation of the mTOR pathway, which may provide a therapeutic opportunity in this distinct subtype of SCLC.
Supported by the ÚNKP-23-4-II-SE-9 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund.

University

Semmelweis University

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

1307

Start

11:00

End

11:10