HOXB13 immunohistochemical expression in prostate cancer and its association with tumor grade and invasiveness at a tertiary Referral Hospital in Western Kenya

Resumo

Prostate cancer remains an important health burden in Kenya, where delayed diagnosis and presentation with advanced disease complicate risk stratification. This study evaluated HOXB13 immunohistochemical expression in archived prostate cancer biopsies and examined its relationship with histopathological grade, pathological stage, perineural invasion and selected prostate-specific antigen (PSA) measures at Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH), Kisumu. A retrospective cross-sectional study was conducted using 96 archived formalin-fixed, paraffin-embedded prostatic biopsy specimens and corresponding clinical records from cases diagnosed between January 2020 and December 2024. HOXB13 was assessed by immunohistochemistry and categorized as 0, 1+, 2+ or 3+ according to the proportion/intensity of staining; low expression was defined as 0–1+ and high expression as ≥2+. Associations were assessed using Pearson's chi-square or Fisher's exact test, while diagnostic agreement and discrimination were examined using sensitivity, specificity, positive predictive value, Cohen's kappa, McNemar's test and receiver operating characteristic analysis. Multivariable logistic regression was used to examine predictors of high-grade disease. Statistical significance was set at p < .05. High HOXB13 expression was associated with International Society of Urological Pathology (ISUP) high grade (p = .001), perineural invasion (p = .019) and pathological stage pT3–pT4 (p = .025). Against Gleason ≥7 as the reference classification, HOXB13 IHC showed 87.3% sensitivity, 84.8% specificity, 91.7% positive predictive value and substantial agreement (κ = 0.71); AUC = 0.86.  Pre-surgical PSA was elevated in 97.9% of cases, and paired analysis showed a significant post-surgical decline (p = .042).  High HOXB13 expression is associated with aggressive histopathological features including high ISUP grade, advanced pathological stage and perineural invasion. The observed sensitivity, specificity and substantial agreement with Gleason-based grading support the potential of HOXB13 immunohistochemistry as an adjunct to conventional histopathological assessment for characterizing aggressive prostate cancer in this referral setting, rather than as a standalone diagnostic test. Further validation is recommended through larger, multi-center prospective studies in Kenya that include benign prostatic hyperplasia and atypical lesions as comparators, correlate HOXB13 protein expression with germline G84E status and clinical outcomes such as biochemical recurrence, and standardize staining and scoring protocols across laboratories. These findings support further validation of HOXB13 IHC as an adjunct to conventional histopathological assessment for characterizing aggressive prostate cancer in Kenyan referral settings. In the interim, there is a need for capacity building in immunohistochemistry, quality assurance and pathologist training at JOOTRH and similar referral hospitals, and for integration of HOXB13 testing into research registries to inform future risk stratification algorithms beyond PSA alone.