Prognostic Value of Apoptosis-Inducing Factor (AIF) in Germ Cell Tumors

Abstract

Apoptosis is a strictly regulated process essential for preservation of tissue homeostasis. This study aimed to evaluate expression of apoptosis inducing factor (AIF) in testicular germ cell tumors (GCTs) and to correlate expression patterns with clinicopathological variables. Formalin-fixed and paraffin-embedded specimens of non-neoplastic testicular tissue and GCTs obtained from 216 patients were included in the study. AIF expression was detected by immunohistochemistry, scored by the multiplicative quickscore method (QS). Normal testicular tissue exhibits higher cytoplasmic granular expression of AIF compared to GCTs (mean QS = 12.77 vs. 4.80, p < 0.0001). Among invasive GCTs, mean QS was the highest in embryonal carcinoma, yolk sac tumor and seminoma, lower in teratoma and the lowest in choriocarcinoma. No nuclear translocation of AIF was observed. Nonpulmonary visceral metastases were associated with lower AIF expression. Metastatic GCTs patients with high AIF expression had better overall survival compared to patients with low AIF expression (HR = 0.26, 95% CI 0.11–0.62, p = 0.048). We observed significantly lower AIF expression in GCTs compared to normal testicular tissue, which is an uncommon finding in malignant tumors. AIF downregulation might represent one of the mechanisms of inhibition of apoptosis and promotion of cell survival in GCTs.

Role of the apoptosis-inducing factor in physiological conditions and in malignant neoplasms

“…Редуцирана експресия на AIF е установена и при други тумори. Letkovska et al (2021) анализират AIF при герминативноклетъчни тумори и установяват редуцирана експресия в туморната тъкан на неинвазивни и инвазивни неоплазми в сравнение с нетуморната тъкан на тестиса, където позитивност се открива в сперматогенните клетки на семиниферните тубули. В зависимост от хистологичния вариант на инвазивните герминативноклетъчни тумори най-висока позитивност има при ембрионален карцином, следван от yolk sac тумор и семином, понижава се при тератома и е най-ниска при хориокарцинома.…”

Amplification of ferroptosis with a liposomal nanoreactor cooperates with low-toxicity doxorubicin apoptosis for enhanced tumor chemotherapy

“…What is worse is that tumor cells usually evolve to protect themselves by enhancing gene mutation, which either blocks apoptosis signal transduction or directly invalidates the apoptosis mechanism after long exposure to apoptosis-inducing drugs. 3 Meanwhile, the DNA damage response also keeps increasing the drug resistance and impairing the efficacy of chemotherapy drugs. 4,5 Therefore, traditional chemotherapy dependent on apoptosis-inducing drugs, like DOX, is no longer an optimal choice for inhibiting tumor growth, and accordingly refined chemotherapy based on novel cell death forms is urgently needed and may pave a promising avenue for tumor therapy.…”