Penile cancer is a rare malignancy in Western Europe and the United States with age-standardized incidence rates (ASR) of 0.1-1.5 per 100,000 men. In Africa, Asia and South America, however, the estimate ASRs are significantly higher with peaks of 2.8 and 3.7 per 100,000 men, in Uganda and Brazil, respectively
The most common histological type of penile carcinoma is the squamous cell carcinoma (95%) which comprises several subtypes such as usual squamous cell carcinoma(48-65%), basaloid (4-10%), warty (7-10%), verrucous (3-8%), papillary (5-15%) and mixed carcinoma (9-10%)
. Although the etiology of penile cancer is not yet fully understood several risk factors, such as poor hygiene and phimosis, lack of circumcision in childhood and history of smoking, have been shown to increase the risk to develop this malignancy
[3–6]. Human papillomaviruses (HPV) have been associated with approximately 47% of invasive penile carcinoma cases with HPV16 and HPV18 as the most common viral genotypes accounting for 60.23% and 13.35%, respectively, of the HPV attributable cases
. Higher rates of HPV positivity have been found in warty-basaloid (82%), basaloid (76%), and warty carcinomas (39%). This observation was indicative of a strong association between the basaloid cell type and presence of HPV
Several studies have reported genetic alterations in tumor suppressor genes and oncogenes, in both HPV-positive and HPV-negative penile cancers, which may have a critical role in tumor carcinogenesis
[9, 10]. STK11 is a 23 kb tumor suppressor gene, mapped to chromosome 19p13.3, which encodes for the serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) or renal carcinoma antigen NY-REN-19
[11, 12]. The STK11 gene is widely expressed in embryonic and adult tissues and the encoded STK11 kinase is an essential regulator of chromatin remodeling, cell cycle arrest, p53-dependent apoptosis, Wnt signaling, cell polarity and energy metabolism
[13–15]. Germ-line mutations of the STK11 gene are associated with Peutz-Jeghers syndrome (PJ)
[11, 12], an autosomal dominant disorder characterized by hamartomatous polyps of the gastrointestinal tract and by a considerably increased risk of cancer in gastrointestinal tract, pancreas, breast, lung, uterus, cervix, ovary and testis
[16–18]. PJ patients are at increased risk to develop cancer particularly at body sites with higher levels of STK11 enzyme in the normal tissue
Somatic mutations of STK11gene have been frequently found in several sporadic tumors, including HPV-related cervical cancer
[20–25]. No studies have been performed on STK11 mutational status in penile carcinoma.
The aim of the present study was to analyze genetic alterations and single nucleotide mutations in exons 1 to 9 of STK11 gene in HPV-positive and HPV-negative penile cancers to possibly establish a relationship between HPV infection and genetic alterations involved in cancer progression.