Simple Summary
Cancer growth and spread are strongly influenced by the surrounding tissue, known as the tumor microenvironment. This environment contains immune cells and connective tissue that can either slow down or promote tumor progression. In this study, we focused on a specific type of immune cell, neutrophils, and on changes in the connective tissue surrounding tumors, known as the desmoplastic reaction. We examined tissue samples from 65 cancer patients to understand how these features relate to tumor aggressiveness and common clinical characteristics. We found that higher numbers of neutrophils were associated with more aggressive tumors and specific connective tissue patterns. In particular, tumors with loose, myxoid connective tissue showed increased neutrophil infiltration. These findings suggest that interactions between immune cells and connective tissue contribute to tumor behavior and help improve future tumor evaluation and risk assessment.
Abstract
Background: The tumor microenvironment (TME), composed of diverse immune and stromal cells, plays a key role in cancer progression. Among its components, tumor-associated neutrophils (TANs) and the desmoplastic reaction (DR) have emerged as important modulators of tumor behavior. While each has been extensively studied, their interrelationship and association with tumor grade and clinicopathological parameters remain unclear. Aim: This hypothesis-generating study aimed to explore the relationship between the presence of TANs, various types of DR, the grade of tumor malignancy, and other fundamental clinicopathological characteristics commonly studied in daily clinical practice. Materials and Methods: The study included a cohort of 65 cancer patients (N = 65). The average number of TANs was recorded. In hematoxylin and eosin (H&E)-stained sections, “hot spots” representing areas with the highest neutrophil density were first identified. The tumor-associated polymorphonuclear neutrophils were then counted in ten consecutive high-power fields (HPFs). In the same specimens, the DR was assessed and classified according to stromal texture. Results: TANs did not follow a normal distribution across any clinicopathological category (p < 0.05). Significant differences in TAN levels were observed among DR types (Kruskal–Wallis H = 9.890, p = 0.007), with higher counts in myxoid compared to mature stroma (Mean Rank = 41.58 vs. 24.80, p = 0.006). TAN levels also varied significantly with tumor grade (H = 22.384, p < 0.001), increasing from Grade 1 to Grade 3 (p < 0.013–0.001). Higher TAN counts were associated with cellular erythroblastic oncogene B2 (c-erbB2) positivity (H = 6.547, p = 0.038), perineural invasion (Mann–Whitney U = 179.5, p < 0.001), and ER/PR negativity (p = 0.016 and p = 0.044, respectively). No significant association was found with necrosis (p = 0.083). A near-significant relationship was identified between DR type and tumor differentiation grade (χ2 = 9.448, p = 0.051), with mature stroma most common in Grade 1 tumors, keloid-like stroma in Grade 2, and myxoid stroma in Grade 3. Conclusions: High TAN levels were linked to aggressive tumor features and specific DR patterns. The association of myxoid stroma with elevated TAN infiltration may reflect a highly aggressive TME. These preliminary results warrant validation in larger, prospective studies.