The intratumour microbiota and neutrophilic inflammation in squamous cell vulvar carcinoma microenvironment.

BACKGROUND: A causal link between microbiota composition (dysbiosis) and oncogenesis has been demonstrated for several types of cancer. Neutrophils play a role in both immune protection against bacterial threats and carcinogenesis. This study aimed to characterise intratumoral bacteria in vulvar squamous cell carcinoma (VSCC) and their putative effect on neutrophil recruitment and cancer progression. METHODS: Clinical material was obtained from 89 patients with VSCC. Next-generation sequencing (NGS) of 16S rRNA and quantitative polymerase chain reaction (qPCR) were used to detect bacterial species in VSCC. To verify neutrophil activation, CD66b expression in tumour specimens was analysed by immunohistochemistry (IHC). Subsequently, IHC was applied to detect the main neutrophil serine proteases (NSPs), cathepsin G (CTSG), neutrophil elastase (ELANE), and proteinase 3 (PRTN3) in VSCC. RESULTS: Fusobacterium nucleatum and Pseudomonas aeruginosa were identified as tumour-promoting bacteria, and their presence was found to be associated with a shorter time to progression in VSCC patients. Furthermore, high abundance of CD66b, the neutrophil activation marker, in VSCC samples, was found to relate to poor survival of patients with VSCC. The selected NSPs were shown to be expressed in vulvar tumours, also within microabscess. The increased numbers of microabscesess were correlated with poor survival in VSCC patients. CONCLUSIONS: Our results show that neutrophilic inflammation seem to be permissive for tumour-promoting bacteria growth in VSCC. The findings provide new therapeutic opportunities, such as based on shifting the balance of neutrophil populations to those with antitumorigenic activity and on targeting NSPs produced by activated neutrophils at the inflammation sites.

Clinical and histopathological factors in patients with cervical cancer allowing to identify candidates for less radical surgery.

OBJECTIVE: To determine clinical and histopathological factors in patients with cervical cancer tumors smaller than 2 cm in order to identify those who could be operated less extensively with preservation of reproductive organs and lower morbidity. MATERIAL AND METHODS: We retrospectively reviewed the records of patients with cervical cancer and a maximum tumor of 2cm in diameter who were qualified for primary surgery in the years 2001-2007 at the Department of Gynecologic Oncology Cancer Center in Warsaw. RESULTS: From the group of 110 operated patients, 96 were included into the study Within the analyzed group the infiltration of the parametrium was found in 4 women (4.2%). All of them had squamous cell cancer; stage IB, grade G3. One patient had a tumor 1.5 cm in diameter and 3 patients had tumors up to 2 cm in diameter. The involvement of lymph nodes was observed in 3 patients with squamous cell carcinoma: in one case the tumor was intermediate grade (G2) and in two cases low grade (G3). The lymph nodes were involved only in patients with tumors greater than 0.5 cm. The lymph vascular space invasion was found in 14 patients (14.7%): in 12 with squamous cell cancer and in 2 with adenocarcinoma. The diameter of the tumor was 0.5-1 cm in 4 women, 1-1.4 cm in 3 women and 1.5-2 cm in the majority (7 women accounted for 29% of all patients in that group). No infiltration of the blood vessels could be seen in all 30 women with tumors smaller than 0.5 cm. We found a statistically significant relationship between the size of the tumor and the incidence of lymph vascular space invasion (p=0.024). CONCLUSION: In selective cases fertility organ preserving surgery is possible and safe. In the group of patients with tumor less than 5 mm in diameter no parametrium involvement or lymph metastases were observed. In such situation cervical conisation can be justified. In well-differentiated (G1) tumors less than 2 cm in diameter less radical surgical procedures can also be performed because no treatment failure has been observed.