# Invasive stratified mucin-producing carcinoma of the cervix: a report of 34 cases of immunohistochemical and clinicopathological findings

**Authors:** Ru Wang, Linlin Zhang, Di Zhao, Ming Liu, Ting Hao, Songsheng Zhang, Lianbao Cao, Hao Yu

PMC · DOI: 10.3389/fonc.2026.1681399 · Frontiers in Oncology · 2026-03-02

## TL;DR

This study examines 34 cases of a rare cervical cancer type, finding it more aggressive than HPV-related cancers and suggesting specific markers for diagnosis.

## Contribution

The study identifies a diagnostic immunohistochemical panel for invasive stratified mucin-producing carcinoma of the cervix.

## Key findings

- ISMC cases show earlier onset, larger tumors, and worse prognosis compared to HPV-associated endocervical adenocarcinoma.
- p16, CK7, and high Ki-67 labeling are consistently positive in ISMC cases.
- Mixed and pure ISMC subtypes have similar clinicopathological features but differ from HPV-related cancers in aggressiveness.

## Abstract

This retrospective study aims to explore the immunohistochemical profile and clinicopathological features of invasive stratified mucin-producing carcinoma (ISMC).

A total of 34 cases of ISMC were selected for this study. ISMCs are classified as either pure or mixed subtype, based on whether they are combined with tumor cells of other pathological types. We compared the clinicopathological features of ISMC with those of human papillomavirus (HPV)-associated cervical endocervical adenocarcinoma, as well as the differences between pure and mixed ISMC, through retrospective analyses.

Approximately 47% (16 out of 34) of the ISMC cases were classified as pure ISMC. There was no significant difference in clinicopathological features between pure ISMC and mixed ISMC. When compared to HPV-associated endocervical adenocarcinoma, ISMC cases presented with an earlier age of onset, larger tumor size, more aggressive biological behavior, and poorer prognosis. All cases exhibited block positivity for p16, positivity for CK7, and a higher Ki-67 labeling index. The expressions of CK5/6, Pax-8, P40, and P63 at the peripheral and mesenchymal junctions of the cancer foci were focally positive. Periodic acid–Schiff (PAS) staining demonstrated intra- and extracellular mucus in the cytoplasm of the tumor cells.

The proportion of mixed ISMC cases is similar to that of pure ISMC. ISMC is more aggressive compared to HPV-associated endocervical adenocarcinoma and is associated with shorter progression-free survival. We recommend the following markers as a diagnostic panel for ISMC: p16, CK7, CK5/6, P40, P63, Pax-8, and PAS.

## Linked entities

- **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029], KRT7 (keratin 7) [NCBI Gene 3855], ck56 (hypothetical protein) [NCBI Gene 310612231], PAX8 (paired box 8) [NCBI Gene 7849], IL9 (interleukin 9) [NCBI Gene 3578], RPE65 (retinoid isomerohydrolase RPE65) [NCBI Gene 6121]
- **Diseases:** cervical cancer (MONDO:0002974)

## Full-text entities

- **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, TP63 (tumor protein p63) [NCBI Gene 8626] {aka AIS, B(p51A), B(p51B), EEC3, KET, LMS}, PAX8 (paired box 8) [NCBI Gene 7849] {aka PAX-8}, KRT7 (keratin 7) [NCBI Gene 3855] {aka CK7, K2C7, K7, SCL}
- **Diseases:** cervical endocervical adenocarcinoma (MESH:D000230), ISMC (MESH:D002288), cancer (MESH:D009369)
- **Species:** Human papillomavirus (species) [taxon 10566]

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12989362/full.md

## References

34 references — full list in the complete paper: https://tomesphere.com/paper/PMC12989362/full.md

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Source: https://tomesphere.com/paper/PMC12989362