Table 3.
Membrane bound mucins in the diagnosis and prognosis of breast cancer.
| Ref. | Mucin | N | Antibody (mAb) | Positivity in Cancer | Controls (% +ve) | Pathologic correlation | Clinical correlation |
|---|---|---|---|---|---|---|---|
| [21] | MU C1 | 68 cancer, 29 Nor, 15 DHWA, 2 DCIS |
SM3 | 74%; C+M | 1.Nor: 59%;C 2.NAT: 59% 3.DHWA: 67% 4.DCIS: 100% |
None to tumor size/stage/grade/E R/HER-2/p53 | None to age. Others NE |
| [10] | MUC1 | 42 FA, 23 NPL, 25 UEH, 7ADH €, 27 Nor | C595, HMFG2,S M3, CT33 | NE | 1. CT33: 92%,M 2. C595: 44%,M 3. HMFG2: 36%,M 4. SM3: 8%,M |
NE | NE |
| [37] | MUC1 | 1447 cancer 0 Nor |
Ma695¥ | 1. Purely L/A: 4.5% 2. L+C: 18.4% 3. C with CMA: 77% |
NE | 1. ER status: +ve correlation: 3. Tumor grade: a. C+M staining: more in high-grade tumors b. L/L+C staining: more in low-grade tumors |
1. Distant metastasis and LN spread: -ve correlation overall. But L staining pattern correlates with vascular invasion, LN spread and distant metastasis. 2. Survival: No relation to overall MUC1 expression. However, C+M staining was associated with lower survival (OS+DFS) than tumors with L staining pattern. 3. Recurrence: ↑ in MUC1-tumors |
| [36] | MUC1 | Axillary LN (17 known +ve, 21 known – ve BC, 51 Nor nodes) | NA (Real time PCR) | 67% sensitive and 82% specific for micrometastasis in LN | NA | NE | NE |
| [25] | MUC1 | 20 cancer (120 margins) | ND | Combination with E-cadherin was 80% sensitive, 100% specific with 100% PPV and 99% NPV by IF on EIOTPs. | Formalin fixed sections were used to confirm EIOTP results | NE | NE |
| [34] | MUC1 | 82 cancer | DF3 (CA15.3), VU-4-H5, PankoMab | Comparison of mAbs: 1. PankoMab: stronger staining in ER+ tumors 2. VU-4-H5: strong staining in LN deposits and higher grade tumors 3. DF3: NS |
NE | 1. PankoMab ↓ staining with ↑ grade (NS) 2. DF3: ↑ staining in Grade 2 than in grade 3 tumors (NS) 3. VU-4H-5:In ER-LN- cases, staining G1>G2; In ER+LN+ cases, staining G2>G3. |
NE |
| [43] | MUC1 | 17 Mucinous and 46 ductal carcinoma | NCL-MUC1-CORE, DF3, HMFG-2, MY.1E12, NCL-MUC1, HMFG-1 | 1. NCL-MUC1-CORE: 98% (IDC) vs. 76% (MC) 2. DF3: 100% (IDC) vs 100% (MC) 3. HMFG-2: 92% (IDC) vs. 88% (MC) 4. MY.1E12: 100% (IDC) vs. 100% (MC) 5. NCL-MUC1: 95% (IDC) vs. 88% (MC) 6.HMFG-1:98% (IDC)vs.65% (MC) |
100% (NAT) | 1. Nor: L staining of ducts and lobules 2. Cancer: C+M (C>M) |
NE |
| [35] | MUC1 | 5 spindle cell BC | - | 100% | NE | 20% were HER2+, 40% PR+ and 90% ER+ | NE |
| [37] | MUC3 | 1447 cancer 0 Nor |
1143/B7 | 91% C:91% C+M:21% |
NE |
1. ER status: -ve correlation with the expression of MUC3 3. Tumor grade: More expression correlates with higher grade |
1. Distant metastasis and LN spread: +ve correlation with vascular invasion, and LN spread 2. Survival: None 3. Recurrence: ↑ in MUC3+ tumors |
| [37] | MUC4 | 1447 cancer 0 Nor |
1G8 | 95% | NE | 1. ER status: None 3. Tumor grade: +ve correlation |
1. Distant metastasis and LN spread: None 2. Survival: None 3. Recurrence: None |
| [22] | MUC4 | 1. Lysates: 8 Nor and 70 tumors. 2. Tissues: 110 Nor, 40 pre-malignant, 286 P & 48 Met BC |
1G8 | 1.IB: 84% 2. IHC: 58% PADC showed ↓ in expression (relative to paired Nor tissue) and 11% had ↑ expression (79% +ve overall). 3. Lobular Ca (68% by IHC) |
Nor breast1. IB: 100%§ 2. IHC: 92% Hyperplasia (100%) DCIS (86%) |
ER/PR/HER-2/p5 3 status: None (both in IB and IHC) | Distant metastasis: had ↑ MUC4 expression than matched primary tumor. |
| [38] | MUC1, 2,4, 5A C and 6 | Six 1° and three metastati c breast SRCC | MUC1 (Ma695) MUC2 (CCP58) MUC4 (1G8) MUC5AC (45M1) MUC6 (CLH5) |
1. MUC1 (100% of P 100% Met) 2. MUC2 (33% of P & 0% Met) 3. MUC6 (17% of P &0% Met) 4. MUC4 and MUC5AC were -ve |
NE | No correlation between MUC16 positivity and nuclear grade | NA |
| [45] | MUC16 | 37 IMPC | CA125 | 40%, L+M | NE | NE | NE |
| [71] | MUC1 | 48 cancer† Unknow number of healthy blood samples | IMS (using anti-MUC1 mAbs) →Multiple × PCR for MUC-1, HER-2, Claudin-7 and GA733-2 | 1. 58% of BC patients with detectable DTCs were MUC1+2. Patients who were MUC1- in the beginning were also –ve on follow-up at 1 year. | None | NE | NE |
| [72] | MUC1 | 63 cancer 14 Nor Blood samples |
IMS (using anti-MUC1 mAbs) to isolate DTCs→ Multiplex PCR for MUC-1, HER-2, MGB-1, GA733-2 and SPDEF | ND | NE | NE | 1. MUC1 positivity ↑ from stage 1 (0%) →Stage 2 (6%) → Stage 3 (33%) 2. It also ↑ from no LN involvement (7%) → N1 (16%) → N2 (33%) 3. Higher positivity in Met (32%) than non-Met (9%) BC. 4. 56% +ve for serum CA15.3 were also MUC1+, while only 8% of CA15.3-samples were MUC1+ |
Recognizes the glycosylated form of MUC1. Similar results were also obtained with an mAb that recognizes the unglycosylated form of MUC1 (Ma552)
Wang et al.[94] using the Ma695 mAb reported a similar observation that MUC1+ breast cancers were more likely to be ER+ and of a lower grade than MUC1- tumors.
Expression was significantly downregulated in tumor tissue compared to adjacent normal breast tissue by IB.
All patients had metastatic BC and had been treated with either Herceptin or chemotherapy prior to drawing of the blood sample. Breast cancer (BC); Primary Adenocarcinoma (PADC); Apical (A); Cytoplasmic (C); Circumferential membrane accentuation (CMA); Granular (G); Invasive micropapillary carcinoma (IMPC); Luminal (L); Membrane (M)Number of samples (N);Lymph node (LN); Primary (P); Normal (Nor) Metastatic (Met) Not examined (NE); Not statistically significant (NS); DCIS, ductal carcinoma in situ; DHWA, ductal hyperplasia without atypia; monoclonal antibody (mAb); polyclonal antibody (pAb); Overall survival (OS), Disease free interval (DFI); Immunoblotting (IB); Immunofluorescence (IF); Enhanced intraoperative touch preps (EIOTP);
Fibroadenoma (F), Non-proliferative lesions (NPL), Usual epithelial hyperplasia (UEH), Atypical ductal hyperplasia (ADH).