# Immunohistochemical expression of CANT1 and B3GNT3 in invasive ductal carcinoma of the breast: diagnostic and prognostic significance in lymph node metastasis

**Authors:** Dalia Mostafa Thabet, Al Shaimaa Wagdy Kassem Abu Bakr

PMC · DOI: 10.1186/s13000-025-01745-9 · Diagnostic Pathology · 2026-01-16

## TL;DR

This study explores the role of CANT1 and B3GNT3 in breast cancer, finding that high expression of these proteins is linked to aggressive cancer features and poor patient outcomes.

## Contribution

The study identifies CANT1 and B3GNT3 as potential prognostic markers for lymph node metastasis in invasive ductal breast carcinoma.

## Key findings

- High CANT1 and B3GNT3 expression correlates with aggressive tumor features like high grade and metastasis.
- B3GNT3 is an independent predictor of poor prognosis in invasive ductal carcinoma.
- Co-expression of CANT1 and B3GNT3 is strongly associated with lymph node metastasis.

## Abstract

Breast cancer is a leading global health concern, with lymph node metastasis (LNM) being a key prognostic factor affecting patient outcomes. Glycosylation-related enzymes such as calcium-activated nucleotidase 1 (CANT1) and Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) have been implicated in tumour progression, yet their roles in breast cancer, particularly invasive ductal carcinoma (IDC), are not well defined. This study investigates the immunohistochemical expression and correlation of CANT1 and B3GNT3 in IDC and their potential role in predicting LNM and clinical outcomes.

Slides from paraffin blocks of 140 IDC cases and 108 corresponding metastatic axillary lymph nodes were stained with CANT1 and B3GNT3 antibodies. Associations between markers’ immunoreactivity and clinicopathological variables were evaluated. Progression-free survival (PFS) was analysed using the Kaplan–Meier method. The prognostic significance of each variable was evaluated using both univariate and multivariate Cox proportional hazards regression analyses.

High CANT1 and B3GNT3 expression was observed in 47.1% and 45.7% of cases, respectively. Both markers were significantly associated with tumour grade, tumour stage, Nottingham prognostic index, lymph node status, lymph node ratio, Her2 status, Ki-67 proliferative index and distant metastasis. A significant positive correlation was found between CANT1 and B3GNT3 expression (p < 0.001). Co-expression of both markers was strongly associated with LNM, along with a significant difference in the expression levels of each marker between primary tumours and corresponding LNM. Univariate analysis showed that tumour grade, stage, ER status and high B3GNT3 expression were all significantly associated with worse PFS. Multivariate Cox regression identified B3GNT3 expression, tumour grade and tumour stage as independent predictors of poor prognosis in IDC. High expression levels of CANT1 and B3GNT3 were associated with reduced PFS across all IDC cases (p = 0.035 and p = 0.001, respectively).

High CANT1 and B3GNT3 expressions are associated with aggressive clinicopathological features in IDC and predict unfavourable outcomes. These markers may serve as potential prognostic indicators and independent predictors of LNM in IDC patients.

## Linked entities

- **Genes:** CANT1 (calcium activated nucleotidase 1) [NCBI Gene 124583], B3GNT3 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3) [NCBI Gene 10331]
- **Diseases:** breast cancer (MONDO:0004989), invasive ductal carcinoma (MONDO:0004953)

## Full-text entities

- **Genes:** CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, CD274 (CD274 molecule) [NCBI Gene 29126] {aka ADMIO5, B7-H, B7H1, PD-L1, PDCD1L1, PDCD1LG1}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, ABCB6 (ATP binding cassette subfamily B member 6 (LAN blood group)) [NCBI Gene 10058] {aka ABC, LAN, MTABC3, PRP, umat}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}, BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, MMRN1 (multimerin 1) [NCBI Gene 22915] {aka ECM, EMILIN4, GPIa*, MMRN}, EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, NR4A1 (nuclear receptor subfamily 4 group A member 1) [NCBI Gene 3164] {aka GFRP1, HMR, N10, NAK-1, NGFIB, NP10}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, RHOA (ras homolog family member A) [NCBI Gene 387] {aka ARH12, ARHA, EDFAOB, RHO12, RHOH12}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, RAC1 (Rac family small GTPase 1) [NCBI Gene 5879] {aka MIG5, MRD48, Rac-1, TC-25, p21-Rac1}, B3GNT3 (UDP-GlcNAc:betaGal beta-1,3-N-acetylglucosaminyltransferase 3) [NCBI Gene 10331] {aka B3GAL-T8, B3GN-T3, B3GNT-3, HP10328, TMEM3, beta3Gn-T3}, CANT1 (calcium activated nucleotidase 1) [NCBI Gene 124583] {aka DBQD, DBQD1, EDM7, SCAN-1, SCAN1, SHAPY}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, COX8A (cytochrome c oxidase subunit 8A) [NCBI Gene 1351] {aka COX, COX8, COX8-2, COX8L, MC4DN15, VIII}
- **Diseases:** neuroblastoma (MESH:D009447), pancreatic adenocarcinoma (MESH:D010190), LNM (MESH:D008207), invasive ductal carcinoma of the breast (MESH:D018270), nodal (MESH:D013611), DCIS (MESH:D002285), LVI (MESH:D009361), HCC (MESH:D006528), Tumor (MESH:D009369), II (MESH:C537730), cervical cancer (MESH:D002583), lymph node (MESH:D000072717), IDC (MESH:D044584), metastasis (MESH:D009362), non-Hodgkin's lymphoma (MESH:D008228), prostate cancer (MESH:D011471), endometrial cancer (MESH:D016889), lung adenocarcinoma (MESH:D000077192), TNBC (MESH:D064726), carcinogenesis (MESH:D063646), Breast cancer (MESH:D001943), breast (MESH:D061325)
- **Chemicals:** uridine diphosphate (MESH:D014530), lipids (MESH:D008055), poly-N-acetyllactosamine (MESH:C037199), xylene (MESH:D014992), citrate (MESH:D019343), 3,3'-diaminobenzidine tetrahydrochloride (-), eosin (MESH:D004801), carbohydrate (MESH:D002241), uridine monophosphate (MESH:D014542), hydrogen peroxide (MESH:D006861), paraffin (MESH:D010232), haematoxylin (MESH:D006416)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Rattus norvegicus (brown rat, species) [taxon 10116], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12866187/full.md

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Source: https://tomesphere.com/paper/PMC12866187