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. 2025 Jul 15;17(7):e88040.
doi: 10.7759/cureus.88040. eCollection 2025 Jul.

Differentiating Neoplastic From Non-neoplastic Gallbladder Lesions Using MUC1 and MUC5AC: An Immunohistochemical Analysis

Umika Gupta  1 , Vijai Singh  1 , Sanjeev Yadav  1
Affiliations

Differentiating Neoplastic From Non-neoplastic Gallbladder Lesions Using MUC1 and MUC5AC: An Immunohistochemical Analysis

Umika Gupta et al. Cureus. .

Abstract

Background: Gallbladder lesions range from benign inflammatory conditions to malignancies, often progressing through pre-neoplastic stages. Accurate histopathological differentiation, particularly in early stages, remains challenging. Mucin proteins MUC1 and MUC5AC have emerged as potential immunohistochemical (IHC) markers for distinguishing neoplastic from non-neoplastic gallbladder pathology.

Material and methods: A cross-sectional study was conducted on 52 formalin-fixed, paraffin-embedded (FFPE) gallbladder specimens from cholecystectomy cases over two years. Routine histopathological evaluation was followed by IHC staining using monoclonal antibodies against MUC1 and MUC5AC. Expression levels were semi-quantitatively scored (0-3) and statistically analyzed in relation to neoplastic status.

Results: Of the 52 cases, 29 (55.8%) were non-neoplastic and 23 (44.2%) were neoplastic, with 91.3% (n = 21) of the latter being malignant. MUC1 expression was significantly higher in neoplastic lesions (p < 0.001), with 73.9% (n = 17) showing strong (score 3) positivity. Conversely, MUC5AC was predominantly expressed in non-neoplastic lesions, with strong expression observed in 55.2% (n = 16) versus 13.0% (n = 3) of neoplastic cases (p < 0.001). MUC1 demonstrated high diagnostic performance for neoplasia (sensitivity 95.7%, specificity 75.9%), while MUC5AC showed moderate performance (sensitivity 69.6%, specificity 72.4%). The inverse expression profiles of these markers effectively differentiated malignant from benign lesions.

Conclusion: MUC1 and MUC5AC exhibit distinct IHC expression patterns in gallbladder pathology. MUC1 is a sensitive marker for neoplastic transformation, whereas MUC5AC is more indicative of benign or early-stage lesions. Their combined application may improve diagnostic accuracy in histologically ambiguous cases. Incorporating these biomarkers into routine pathology practice may aid early detection and better clinical decision-making. Further large-scale studies are needed to validate their prognostic significance.

Keywords: biomarkers; cholecystitis; gallbladder neoplasms; immunohistochemistry; muc1; muc5ac.

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Conflict of interest statement

Human subjects: Informed consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Ethics Committee, Hind Institute of Medical Sciences, Sitapur, India issued approval MD/MS(20)/RD/06-22. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Heatmap showing MUC1 and MUC5AC expressions across all histological cases
Each row represents a case labelled by its histology type and lesion category (neoplastic or non-neoplastic). Colors reflect expression intensity: red shades indicate higher expression and blue shades indicate lower expression.
See this image and copyright information in PMC

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