Background
Methods
Patients and selection of cases
Immunohistochemistry
Antibody
|
Clone
|
Dilution
|
Manufacturing company
|
---|---|---|---|
Galectin-3
| 9C4 | 1:200 | Novocastra, Newcastle, UK |
HBME-1
| HBME-1 | 1:50 | DakoCytomation, Glostrup, Denmark |
CK19
| b-170 | 1:200 | Novocastra, Newcastle, UK |
Cyclin D1
| SP 4 | 1:25 | Thermo Scientific, Fremont, CA, USA |
Ki67
| MIB 1 | 1:100 | DakoCytomation, Glostrup, Denmark |
Evaluation of immunostaining
Fluorescent in-situ hybridization
Statistical analysis
Results
S.No
|
Age at presentation
|
Sex
|
Presenting complaints
|
Diagnosis since
|
Prognosis
|
---|---|---|---|---|---|
1 | 63 years | M | Nodular goitre | 10 years | No recurrence |
2 | 56 years | F | Nodular goitre | 5 years | No recurrence |
3 | 55 years | F | Nodular goitre | 5 years | No recurrence |
4 | 57 years | F | Nodular goitre | 10 years | No recurrence |
5 | 50 years | F | Nodule with dysphonia | 3 years | No recurrence |
6 | 50 years | F | Multinodular goitre | 13 years | No recurrence |
7 | 39 years | F | Multinodular goitre | 3 years | No recurrence |
8 | 37 years | M | Mutinodular goitre | 5 years | No recurrence |
9 | 36 years | F | Nodule with hepatitis C | 9 years | No recurrence |
10 | 34 years | F | Multinodular goitre | 13 years | Lost to follow up |
11 | 27 years | F | Nodular goitre | 11 years | No recurrence |
12 | 17 years | F | Nodular goitre | 7 years | No recurrence |
13 | 13 years | F | Nodular goitre | 6 years | No recurrence |
Immunohistochemical results
Variant
|
FVPTC
|
WDT-UMP lesion
|
Papillary microCa
|
Metastatic papillary Ca
|
---|---|---|---|---|
Galectin-3
| 08/13 | 04/13 | 09/13 | 13/13 |
HBME-1
| 10/13 | 10/13 | 12/13 | 13/13 |
CK19
| 11/13 | 11/13 | 11/13 | 13/13 |
Variants of PTC
|
Percentage of Ki67 immunolabelled tumour cells
| |||
---|---|---|---|---|
No staining
|
Grade 1 (<1%)
|
Grade 2 (1–5%)
|
Grade 3 (6-20%)
| |
FVPTC (n = 13)
|
1
|
3
|
3
|
6
|
WDT-UMP lesion (n = 13)
|
0
|
2
|
6
|
5
|
Papillary microCa (n = 13)
|
2
|
3
|
6
|
2
|
Metastatic papillary Ca (n = 13)
|
0
|
0
|
2
|
11
|
Variants of PTC
|
Percentage of cyclin D1 immunolabelled tumour cells
| |||
---|---|---|---|---|
No staining
|
Grade 1 (<25%)
|
Grade 2 (25-50%)
|
Grade 3 (>50%)
| |
FVPTC (n = 13)
|
1
|
4
|
2
|
6
|
WDT-UMP lesion (n = 13)
|
0
|
3
|
3
|
7
|
Papillary microCa (n = 13)
|
2
|
4
|
2
|
5
|
Metastatic papillary Ca (n = 13)
|
0
|
2
|
2
|
9
|
FISH results
Discussion
Conclusions
Take home message
-
Cyclin D1 was identified as a strong candidate diagnostic marker for PTC and its variants, including papillary microcarcinomas and also the WDT-UMP lesion. The recognition of WDT-UMP using cyclin D1 as a marker is a first as per the available English literature.
-
HBME-1 was immunolabelled at the membrane in most cases of the PTC variants and also in the WDT-UMP lesion but not in the normal thyroid tissue or the benign adenomatoid areas.
-
Identification of a biomarker that is consistently present in invasive as well as the WDT-UMP lesion and absent in the adjacent normal thyroid tissue provides evidence that this group of lesions is a reliable precursor of FVPTC. Increased expression of cyclin D1 and amplification of its gene along with immunolabelling of HBME-1 in WDT-UMP areas showing cytological features of papillary thyroid carcinoma within follicular adenomatoid nodules suggest that these areas could correspond to a precursor lesion of follicular variant of papillary thyroid carcinoma.