# Tumor Microenvironment and Dermatological Conditions in Prostate Cancer
###### Abstract  
Tumor initiation, progression, and invasion are closely related to the tumor microenvironment. Inflammation can modulate the activity of the cells in the TME and contribute to all stages of tumor development. The etiopathogenesis of cutaneous manifestations associated with prostate cancer is unclear. The cutaneous phenotype associated with prostate cancer could be supported by intratumoral heterogeneity, the remodeling of interactions in the tumor microenvironment, and the dynamics of the epithelial-mesenchymal transition. Among the urinary system cancers, prostate cancer presents few cutaneous signs and symptoms, most being diagnosed in the advanced stages of the disease. In this review, we analyze the cutaneous events associated with prostate cancer, represented by direct or indirect manifestations of the primary malignancy and the skin toxicities caused by oncological medications.  
prostate cancer; tumor microenvironment; inflammation; associated cutaneous manifestations +
Footnote †: journal: Medical Cancer  
0000-0001-9965-3300]C. D. Ene  
0000-0001-9965-3300]T. Ene  
0000-000  
tumor of uncertain malignant potential and prostatic stromal sarcoma) [4]. The vast majority are adenocarcinomas (95%) and have an acinar origin and only a small number originate at the ductal level. Most patients are diagnosed in the early stages, but it should be borne in mind that the morbidity associated with the therapy is significant [5]. The prostate gland is highly prone to cancer, showing higher malignancy rates compared to other urogenital structures. Prostate cancer development is linked to embryonic growth processes, particularly androgen hormone signaling, such as testosterone, and potentially involves other pathways like Sonic Hedgehog (Shh) and Gli-1 oncogene expression, which may drive tumor growth [6].  
The main risk factors are age, family history, and race. The risk increases significantly after the age of 55, the highest risk being recorded between 70 and 74. Epidemiological studies show that among African Americans the risk of developing PCa is 60% higher than among whites. Also, among these individuals, the mortality rate is much higher. In addition, genetic factors play a significant role. There is evidence supporting the contribution of an individual's genetic profile to the genesis and progression of PCa. BRCA genes, HOX genes, ATM gene, RNase L (HPC1, lq22), MSR1 (8p), and ELAC2/HPC2 (17p11) are used as biomarkers for PCa [7]. A series of environmental factors have been reported in the development of PCa such as smoking, diet, obesity, and physical activity [8; 9]. PCa is often detected in asymptomatic patients through elevated prostate-specific antigen (PSA) levels during screening. A PSA test associated with digital rectal examination helps detect prostate cancer at an early stage [10]. It can also be found incidentally during procedures for benign prostatic hyperplasia. When it is diagnosed in a symptomatic stage, PCa often presents with urinary symptoms, back pain, or blood in the urine. Advanced PCa can spread locally, through the lymphatic system or blood and metastasize to bone, the lungs, and the liver, metastasis to bone being the most commonly encountered [11].  
Although prostate cancer (PCa) is the second most common urological malignancy after renal cancer, associated with cutaneous involvement, instances where a skin manifestation is classified as a paraeoplastic syndrome linked to this malignancy are rarely reported in the literature [12; 13]. PCa-induced cutaneous manifestations cause considerable discomfort, and usually indicate advanced disease [14]. In the first part, this paper provides a review of the mechanisms of PCa progression, followed by a summary of the cutaneous events related to PCa, which may reflect direct metastatic spread, non-metastatic manifestations of malignancy, or the consequences of oncological treatment.