Tumor budding in cervical carcinoma: Associations with some clinical and pathological factors

Abstract

Received 2020-01-24 Received in revised form 2020-02-13 Accepted 2020-05-05 INTRODUCTION Cervical cancer is a main cause of cancer-related deaths in women in low-income countries (1). Predicted European cervical cancer prevalence in 2018 was 27.9 by age standardised rate (ASR) per 100 000 inhabitants, and with highest recorded ASR in Latvia (32.2), Estonia (32.0) and Romania (31.2) (2). Squamous, adenoand adenosquamous types of carcinoma are major histologic types of cervical carcinoma, squamous carcinoma being the most common among all other types (3,4). It is well known that both squamous and adenocarcinoma of the cervix are associated with human papillomavirus infection, that plays vital role in pathogeneses of pre-neoplastic and neoplastic lesions of the cervix. (5). Cervical squamous cell carcinoma is often unpredictable disease, starting from slowly progressing to aggressive form (6). The histologic grade of cervical carcinoma is, primarily based on keratinization, cytological features, mitotic activity, as well as pattern of invasion (7-10). However, these studies have not affirmed the prognostic significance of any proposed grading systems. Nowadays, grading systems taking into account pattern on the invasive front of the tumor have been proposed (11). The latest one, 3-stage scoring system of infiltrative growth of cervical carcinoma was proposed with: closed, fingerand spray-like pattern of invasion (Figure 1) (11). Closed pattern of invasion is consisted of solid, cohesive areas of atypical cells. A finger-like pattern of invasion is characterized by trabecular systems with spherical edges at the same time as the spray-like pattern of invasion is defined by the small cell groups or single cells infiltrating cervical stroma (12-14). In case of adenocarcinoma, invasive front is divided into 3 distinct categories: group-A is defined by glandular shape without presence of single invasive cells, group-B is consisted of trabecular structures accompanied with early invasion of surrounding stroma and group-C is described by presence of solid structure or diffuse infiltration (4). Tumor budding, first described in 1950s, was defined as a remote single cancer cell or microscopic small cell cluster in the front of the invasive margin of the tumor (15,16). Those isolated cancer cells on the invasive front of the tumor were related to more aggressive form of disease. Histologically, tumor budding is explained as a sign of cancer cell motility (17). These motile single cancer cells infiltrate surrounding tissues and in this process they are able to infiltrate vascular spaces, this being the critical point in initiating haematogenous spread of disease and development of metastases (17). Based on results of our study tumor budding should be considered as a strong prognostic factor for poor prognosis in cervical carcinoma and viewed on as a primary step of metastatic process.