Relationship between tumor size and aggressive pathological features in gastric adenocarcinoma

Authors

Abstract

AimGastric adenocarcinoma shows heterogeneous biological behavior, and its prognosis is influenced by multiple clinicopathological factors. Tumor size is an easily measurable parameter, but its relationship with pathological indicators of aggressiveness remains incompletely defined. This study aimed to evaluate the association between tumor size and aggressive pathological features in patients who underwent surgery for gastric adenocarcinoma.
MethodsThis single-center retrospective study included 58 patients who underwent curative resection for gastric adenocarcinoma at Gaziantep City Hospital between 03/02/2024 and 01/03/2026. Demographic, clinical, surgical, and pathological data were obtained retrospectively. Associations between tumor size and pT stage, pN stage, pathological stage, number of metastatic lymph nodes, lymph node ratio, lymphovascular invasion, perineural invasion, and histological grade were analyzed.
ResultsA total of 58 patients were included. Tumor size showed significant positive correlations with pT stage (rho=0.263; p=0.046), pN stage (rho=0.298; p=0.023), pathological stage (rho=0.293; p=0.026), number of positive lymph nodes (rho=0.328; p=0.012), and lymph node ratio (rho=0.288; p=0.028). In logistic regression, each 1-cm increase in tumor size was associated with perineural invasion (OR=1.29; p=0.036). Patients with tumors >5 cm had higher rates of perineural invasion, distant metastasis, positive lymph node count, and lymph node ratio.
ConclusionIn gastric adenocarcinoma, tumor size may serve as a practical parameter associated with pathological indicators of aggressiveness. When interpreted together with advanced tumor invasion, increased nodal burden, and invasive histopathological features, it may contribute to a better understanding of tumor biology. These findings should be confirmed in larger multicenter studies.

Keywords

Introduction

Gastric cancer remains one of the leading causes of cancer-related morbidity and mortality worldwide.¹ Despite progress in diagnosis and treatment, a considerable proportion of patients are still diagnosed at an advanced stage, which adversely affects long-term oncological outcomes.^1,2 Therefore, a more detailed definition of the clinicopathological factors associated with prognosis remains important.
Gastric adenocarcinoma demonstrates heterogeneous biological behavior. In current classification systems, histological subtype, differentiation grade, and morphological characteristics are key components in the evaluation of tumor biology.^3,4 In addition, accurate pathological assessment of tumor invasion depth, lymph node involvement, and metastatic spread after surgery is essential for staging and treatment planning.⁵
Although the TNM staging system remains the main framework for prognostic assessment in gastric cancer, anatomical extent alone does not always fully reflect biological aggressiveness.⁵ For this reason, pathological parameters such as lymphovascular invasion, perineural invasion, and metastatic nodal burden, as well as easily measurable morphological variables such as tumor size, have increasingly drawn attention.^5,6 Larger tumor size has been reported to be associated with deeper wall invasion, increased lymph node metastasis, and other adverse pathological features.⁶
However, studies directly evaluating the relationship between tumor size and multiple aggressive pathological indicators in gastric adenocarcinoma remain limited. Therefore, this study aimed to investigate the association between tumor size and aggressive pathological features in patients who underwent surgery for gastric adenocarcinoma.

Materials and Methods

This was a single-center retrospective observational study conducted at Gaziantep City Hospital. Adult patients who underwent surgery for gastric cancer between 03/02/2024 and 01/03/2026 and had histopathologically confirmed gastric adenocarcinoma were screened. Only patients who underwent total or subtotal gastrectomy with curative intent were included. Availability of tumor size and core histopathological parameters in the pathology report was required for inclusion.
Patients with incomplete demographic, clinical, or pathological data were excluded. Cases lacking pT stage, pN stage, total lymph node count, metastatic lymph node count, lymphovascular invasion, perineural invasion, or histological differentiation data were excluded. Non-adenocarcinoma gastric tumors, patients operated on in another center and followed only at our institution, patients who underwent only diagnostic or palliative procedures due to distant metastasis at baseline, patients who underwent emergency surgery, patients younger than 18 years, and duplicate records were also excluded.
Data were obtained retrospectively from hospital archives, the electronic medical record system, operative notes, and pathology reports. Recorded demographic variables included age, sex, body mass index, ASA score, and comorbidities. Clinical variables included diagnosis date, tumor location, preoperative CEA and CA 19-9 levels, clinical stage, and neoadjuvant treatment status. Surgical variables included surgical approach, operation date, resection type, D2 lymph node dissection status, operative time, intraoperative blood loss, and intraoperative complications. Pathological evaluation included tumor size, macroscopic and histological tumor type, differentiation grade, pathological T and N stage, total lymph node count, metastatic lymph node count, lymphovascular invasion, perineural invasion, and pathological stage. Postoperative complications and Clavien-Dindo grades were also recorded. Follow-up data included adjuvant treatment, local recurrence, peritoneal recurrence, and distant metastasis.
The primary independent variable was tumor size. Tumor size was evaluated both as a continuous variable and categorically in subgroup analyses to facilitate clinical interpretation. The primary outcome was the association between tumor size and pathological indicators of aggressiveness, including pT stage, pN stage, pathological stage, number of positive lymph nodes, lymph node ratio, lymphovascular invasion, perineural invasion, and histological grade.
Ethical ApprovalThis study was approved by the Non-Interventional Clinical Research Ethics Committee of Gaziantep City Hospital (Date: 27.03.2026, Decision No: 528/2026).
Statistical AnalysisStatistical analyses were performed using IBM SPSS Statistics for Windows (IBM Corp., Armonk, NY, USA). Continuous variables were summarized as mean ± standard deviation or median (interquartile range [IQR]) according to data distribution. Categorical variables were presented as number and percentage. Spearman correlation analysis was used to evaluate the relationship between tumor size and ordinal or continuous pathological variables. Univariable binary logistic regression analysis was performed to examine the association between tumor size and the presence of perineural invasion, lymphovascular invasion, and high-grade histology. For subgroup analysis, patients were divided into two groups according to tumor size (≤5 cm and >5 cm). Continuous variables were compared using the Mann–Whitney U test, and categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. All tests were two-sided, and a p value of <0.05 was considered statistically significant.
Reporting GuidelinesThis study was reported in accordance with the STROBE guideline.

Results

A total of 58 patients with gastric adenocarcinoma were included. Forty-seven patients (81.0%) were male and 11 (19.0%) were female. The median age was 62 years (interquartile range [IQR]: 56–69.5), and the median body mass index was 26.0 kg/m² (IQR: 24.2–27.3). Baseline demographic, clinical, and pathological characteristics are summarized in Table 1.
Tumor size was evaluated in relation to pathological aggressiveness using correlation and regression analyses. Tumor size showed a statistically significant positive correlation with pT stage (rho=0.263; p=0.046). Similarly, significant positive correlations were observed between tumor size and pN stage (rho=0.298; p=0.023), pathological stage (rho=0.293; p=0.026), number of positive lymph nodes (rho=0.328; p=0.012), and lymph node ratio (rho=0.288; p=0.028). No significant association was observed between tumor size and histological grade (rho=0.204; p=0.125).
In logistic regression analysis, each 1-cm increase in tumor size was associated with the presence of perineural invasion (OR=1.29; 95% CI: 1.02–1.64; p=0.036). Although increasing trends were observed for lymphovascular invasion and high-grade histology, these associations did not reach statistical significance (OR=1.22; 95% CI: 0.98–1.52; p=0.073 and OR=1.24; 95% CI: 0.98–1.58; p=0.076, respectively). Correlation, logistic regression, and subgroup comparison results are summarized in Table 2.
For subgroup analysis, patients were divided into two groups according to tumor size (≤5 cm and >5 cm). Perineural invasion positivity was significantly higher in patients with tumors >5 cm (75.0% vs 34.6%; p=0.005). The rate of distant metastasis during follow-up (25.0% vs 3.8%; p=0.033), median number of positive lymph nodes (5 vs 4; p=0.030), and median lymph node ratio (0.227 vs 0.151; p=0.047) were also significantly higher in the >5 cm group. Lymphovascular invasion was more frequent in the larger tumor group, but the difference was not statistically significant (68.8% vs 42.3%; p=0.079). Similarly, no significant difference was found in the rate of high-grade tumors between the two groups (68.8% vs 57.7%; p=0.551).

Discussion

In this study, we evaluated the relationship between tumor size and pathological indicators of aggressiveness in patients undergoing surgery for gastric adenocarcinoma. Our findings suggest that increasing tumor size may coexist with more advanced pathological features. Previous studies have similarly reported that larger tumors may demonstrate more unfavorable biological behavior in gastric cancer.⁷
Interest in the prognostic value of morphological indicators reflecting tumor burden has increased in recent years. Studies examining the association between tumor volume or tumor size and survival have shown that increased tumor burden may be related to more advanced disease and poorer outcomes.⁸ In this context, tumor size may be considered not merely a descriptive measure, but also a variable reflecting tumor biology.
In our series, the relationship between tumor size and pT stage, pN stage, and nodal burden was notable. The literature also indicates that lymph node metastasis, invasion depth, and lymphovascular invasion are closely associated with aggressive biological behavior in gastric cancer.^9,10,11 These data support the biological plausibility of the associations observed in our cohort.
Lymphovascular invasion and perineural invasion are well-recognized histopathological indicators of aggressive tumor behavior in gastric adenocarcinoma. Several studies have shown that lymphovascular invasion is associated with more advanced disease characteristics and poorer oncological outcomes.^12,13,14 Likewise, perineural invasion has been linked to aggressive behavior and adverse prognosis.^15,16 In our study, the higher frequency of these invasive pathological features in patients with larger tumors suggests that tumor size may reflect more than macroscopic extent alone.
Recent studies have increasingly emphasized the combined assessment of multiple pathological aggressiveness markers in gastric cancer. Tumor size, invasion depth, nodal metastasis, lymphovascular invasion, and perineural invasion appear to be complementary parameters rather than isolated findings.^{14,15,16,17,18,19} In particular, risk factors for lymph node metastasis reported in Western series further support the clinical relevance of integrated pathological assessment.¹⁹ When interpreted together, these variables may contribute to a more integrated understanding of tumor biology and risk stratification.
Our findings should be interpreted in light of the study design. The retrospective nature and single-center setting limit generalizability. In addition, the absence of survival analysis prevented direct evaluation of the prognostic effect of tumor size on long-term oncological outcomes. Nevertheless, the present study supports the view that tumor size is a practical and clinically accessible parameter that may contribute to pathological risk assessment in gastric adenocarcinoma.

Limitations

This study has several limitations. First, its retrospective and single-center design limits external validity and introduces the possibility of selection bias. Second, the sample size was relatively small, which may have reduced the statistical power for some subgroup comparisons. Third, survival analyses were not performed; therefore, the prognostic impact of tumor size on long-term outcomes could not be directly assessed. Finally, because the study relied on medical records and pathology reports, unmeasured confounding and incomplete documentation cannot be fully excluded.

Conclusion

In gastric adenocarcinoma, tumor size appears to be associated with pathological indicators of tumor aggressiveness. In the present study, larger tumor size was linked particularly to deeper tumor invasion, greater nodal burden, and more invasive pathological features.
From a clinical perspective, tumor size may contribute to risk stratification when interpreted together with other clinicopathological variables in the preoperative and postoperative setting. However, it should be regarded as a complementary parameter rather than a stand-alone determinant.
Overall, our findings suggest that tumor size may be a practical variable that helps characterize aggressive tumor biology in gastric adenocarcinoma. Larger multicenter studies with long-term follow-up are needed to validate this relationship.

Declarations

Abbreviations

ASA: American Society of Anesthesiologists
CA 19-9: Carbohydrate Antigen 19-9
CEA: Carcinoembryonic Antigen
CI: Confidence Interval
IQR: Interquartile Range
OR: Odds Ratio
SPSS: Statistical Package for the Social Sciences
STROBE: Strengthening the Reporting of Observational Studies in Epidemiology

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About This Article

Received:

May 7, 2026

Accepted:

June 10, 2026

Published Online:

June 21, 2026