الفهرس 
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Abstract
Thyroid cancer is the most common type of endocrine-related cancer
representing the third fastest rising cancer diagnosis in the United States. In Egypt,
it represents 80.3% of endocrine neoplasms and 2.6% of total malignancies.
Papillary thyroid carcinoma (PTC) represents the most common histologic type
of thyroid carcinoma with increase of its incidence nowadays.
Diagnosis of PTC, is not always straightforward because some lesions
exhibited equivocal nuclear features making the distinction of benign from
malignant lesions is difficult; papillary and follicular architectures together with
nuclear irregularity may be seen both in benign and malignant lesions. Also
thyroid neoplasms with follicular patterns as follicular variant of papillary thyroid
carcinoma, follicular adenoma and follicular carcinoma often pose difficulties in
accurate diagnosis during the assessment of cytological and histologic specimens.
Trophoblastic cell surface antigen (TROP-2) was first identified as a cell surface marker for trophoblast cells. The gene that codes for TROP-2 is called,
tumor-associated calcium signal transducer 2 (Tacstd2), that is found on
chromosome 1p 32. TROP-2 stimulates multiple signaling pathways, the most
important of which is MAPK signaling pathway. TROP-2 was subsequently
reported to be over-expressed in a variety of human carcinomas and its overexpression
is associated with tumor aggressiveness and poor prognosis. Few
studies have verified the diagnostic power of TROP2 in PTC suggesting that it
could be a potential novel immunohistochemical marker for identification of
both classic and follicular variants of PTC.
Cytokeratin 19 is an acidic type I cytokeratin which is the smallest (40 kDa)
member of this group of family proteins. Its action as intermediate filament could
be important for structural rigidity, regulating signaling pathways and mediating cell apoptosis, cell cycle arrest, tumor invasion, and metastasis. In the thyroid
gland, normal follicular epithelium usually has shown no detectable CK19
expression in comparison to strong and diffuse staining pattern of CK19 in PTC.
The aim of this study is to assess the diagnostic value of TROP-2 and CK19
expression in differentiating papillary thyroid carcinoma from other mimickers
both singly and in combination
This retrospective study was conducted on 77 paraffin embedded thyroid
gland specimens (56 PTC and 21 non-malignant), collected from the archives of
Pathology Department, Faculty of Medicine, Menoufia University, spanning
the period between January 2014 and January 2018. They were
selected, according to the histopathological diagnosis.
Twelve fine needle aspiration cytology (FNAC) specimens were aspirated
with cell block preparation and were assessed by Thy system
Regarding non-malignant cases (suspicious group), The mean age was 36.80
± 17.45 and ranged from 19 to 75 years with 31 years as a median value. 85.7%
(18 cases) were females and 14.3% (3cases) were males. Six cases (28.57%)were
follicular adenoma, 8 cases were multinodular goiter (MNG) (38.09%), 5 cases
were Hashimoto thyroiditis (23.80%) and 2 cases were Grave’s disease (9.52%)
Regarding PTC group, patients’ age ranged between 10 and 75 years with a
mean± SD of 42.23 ± 16.82 and a median of 38.5 years. Forty cases (71.4%) were
females and the remaining sixteen cases (28.6%) were males. Thirty six cases
were received as total thyroidectomy (64.3%) whereas 20 (35.7%) cases as
hemithyroidectomy specimens. The mean size of tumor was 2.72 ± 2.17cm and
ranged between 0.2 to 10 cm with 1.95 cm as a median. Twenty nine PTC cases
were of T1 stage (51.8%), 15 cases were of T2 stage (26.8%) and lastly 12 cases
were of T3 stage (21.4%). Eighteen out of 23 PTC cases (78.3%) with known lymph node status had positive nodal invasion and 5 cases (21.7%) were negative.
Thirty eight PTC cases were presented by single tumor nodule (67.9%) and eighteen cases presented by more than one nodule (multifocal) (32.1%). Thirty
five cases were classic papillary thyroid carcinoma type (CVPTC) (62.5%) and
21 cases were follicular variant (FVPTC). Forty seven cases developed tumor on
a background of multinodular goiter (83.9%), while 9 cases showed Hashimoto
thyroiditis in the background (16.1%).
Immunoreactivity of TROP-2 in non-malignant cases revealed negative
expression in 17 out of 21 cases and only four cases were TROP-2 positive. The
mean total estimated score (TES) of positive cases was 0.81 ± 1.8 and ranged
from 0 to7 with a median of 0. The intensity of TROP-2 positivity was strong in
two cases (50%), moderate in one case (25%) and mild in one case (25%). The
percentage of TROP-2 positivity ranged from 0-30% with a mean ± SD of 3.10
± 7.66 and a median of 0. While the calculated H score ranged from 0-70 with a mean±SD of 7.86 ± 19.59 and a median of 0.
Regarding PTC cases; TROP-2 was positive in 40 out of 56 malignant cases
(35 classic and 5 FVPTC). The TES ranged from 0 to 12 with a mean± SD of 5.93
± 4.56 and a median of 7. The intensity of TROP-2 staining was strong in 24 out
of 40 positive cases (60%), moderate in 12 cases (30%) and mild in only 4 cases
(10%) . The mean percentage of TROP-2 expression was 45.07± 41.64 that ranged
from 0 to 100% with a median of 30. By calculating TROP-2 H score mean ± SD,
it was 108.20± 107.19 and ranged from 0 to 290 with a median of 67.5
TROP-2 positivity, TES score, percentage of expression and H score mean
and median values were significantly higher in PTC compared to non-malignant
cases. The sensitivity of TROP-2 expression was 71% with specificity of 81% in
total PTC cases, that was increased to 100% sensitivity and 81% specificity in
classic variant PTC. The sensitivity declined to 23% with fixed specificity at 81% in FVPTC. Application of ROC curve to determine the best cut off point of TROP-
2 TES, percentage of expression and H score in total PTC together with CVPTC
cases was not effective and only TROP-2 positivity was considered in diagnosis.