I Gusti Ayu Made Putri Hitasari, I Nyoman Gede Budiana, I Gede Sastra Winata, I Nyoman Bayu Mahendra, Made Bagus Dwi Aryana, Kade Yudi Saspriana

High p53 protein expression as a risk factor for poor neoadjuvant paclitaxel-carboplatin chemotherapy response in stage IB3, IIA2, and IIB cervical cancer

Introduction

High p53 protein expression as a risk factor for poor neoadjuvant paclitaxel-carboplatin chemotherapy response in stage ib3, iia2, and iib cervical cancer. High p53 expression predicts poor response to neoadjuvant paclitaxel-carboplatin chemotherapy in stage IB3-IIB cervical cancer. Aids pre-treatment risk stratification.

Abstract

Introduction: Expression of the p53 protein plays a critical role in the regulation of cell proliferation, apoptosis, and genomic stability, which has been implicated in chemoresistance in cervical cancer. This study aimed to evaluate high p53 expression is a risk factor for poor response to neoadjuvant paclitaxel-carboplatin chemotherapy in stage IB3, IIA2, and IIB cervical cancer. Methods: Nested case-control study at Prof. Dr. I G. N. G. Ngoerah General Hospital, Denpasar (October 2022-April 2023). Cases were FIGO 2018 IB3, IIA2, IIB patients with poor response by the response evaluation criteria in solid tumours (RECIST) 1.1 after three 3 to 4-weekly cycles of paclitaxel-carboplatin; controls received the same regimen with good response. p53 expression was assessed by immunohistochemistry (IHC). High p53 was defined by a semi-quantitative score >7. Association with response was tested using Pearson’s chi-square and expressed as odds ratios (OR) with 95% confidence intervals (CI) and p-value<0.05. Results: Fifty-six patients were analyzed (28 cases; 28 controls). Baseline characteristics (age, parity, body mass index (BMI), tumor size, histologic grade, histology) were comparable (p>0.05). High p53 expression occurred in 25/28 cases (89.3%) versus 10/28 controls (35.7%). High p53 was strongly associated with poor response (OR 8.33; 95% CI 3.60-62.39; p<0.001). Representative case sections showed strong nuclear staining in 50-95% of tumor cells; control sections showed 10-40% or absent staining. Conclusions: High p53 expression is a significant predictor of poor response to neoadjuvant paclitaxel-carboplatin in stage IB3-IIB cervical cancer. p53 immunohistochemistry may aid pre-treatment risk stratification and inform therapeutic planning.

Review

This study addresses a clinically important question regarding the role of p53 expression as a predictor of response to neoadjuvant paclitaxel-carboplatin chemotherapy in locally advanced cervical cancer. Utilizing a nested case-control design, the authors rigorously assessed p53 expression via immunohistochemistry in patients classified by RECIST 1.1 response. The key finding—a strong association between high p53 expression and poor chemotherapy response (OR 8.33, p<0.001)—is highly significant and suggests that p53 status could serve as a valuable biomarker for pre-treatment risk stratification and therapeutic planning. The clear and concise presentation of results, including comparable baseline characteristics between cases and controls, enhances the credibility of the reported association. The strengths of this research lie in its focused approach to a critical clinical challenge: identifying patients less likely to benefit from standard neoadjuvant chemotherapy. The use of standardized criteria for chemotherapy response (RECIST 1.1) and a readily available, cost-effective method for biomarker assessment (IHC for p53) makes the findings potentially translatable to routine clinical practice. Furthermore, the careful matching of baseline patient characteristics between the good and poor response groups minimizes confounding, strengthening the observed association between p53 expression and treatment outcome. The statistically robust results, despite the moderate sample size, underscore the potential clinical utility of this biomarker. While the study provides compelling evidence, it is important to consider its limitations and future directions. The relatively small sample size (n=56) and the single-center design, though yielding significant results, warrant validation in larger, multi-institutional cohorts to enhance generalizability and refine the precision of the odds ratio. Future research should ideally involve prospective studies to further confirm the predictive utility of p53 expression and explore whether incorporating this biomarker into treatment algorithms can lead to improved patient outcomes. Additionally, investigating the specific molecular mechanisms by which p53 contributes to chemoresistance in this context, beyond just expression levels (e.g., distinguishing between mutant and wild-type p53 accumulation), would provide deeper biological insights and potentially identify novel therapeutic targets.

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