الفهرس 
TitleOnly 14 pages are availabe for public view
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Abstract
PTC is the most common thyroid malignancy with a significant increasing incidence in the last four decades around the world. The pathological diagnosis of PTC in both cytological and histological specimens is based upon the demonstration of typical nuclear morphology with conventional hematoxylin and eosin (H & E) stained sections. But many studies indicated that differentiation of PTC from benign thyroid lesions based on their morphology is often problematic. Ancillary studies such as immmunohistochemistry may be helpful, but till now there is no 100% consistent markers, that distinct between PTC and other follicular thyroid lesions.
The present study aimed by using tissue microarray to evaluating immunohistochemical expression of neural cell adhesion molecule (NCAM / CD56) and emerin as potential diagnostic markers in papillary thyroid cancer versus benign thyroid lesions & their correlation with different clinicopathologica parameters.
To achieve of this aim 100 retrospective paraffin-embedded thyroid specimens divided as; 60 paraffin blocks of primary PTC, 30 paraffin blocks of benign thyroid lesions and10 paraffin blocks of normal thyroid tissue were collected from the department of pathology, Medical Research Institute, Alexandria University, Egypt, during the period between from 2011-2015.
In currant work, TMA blocks were retrieved from the paraffin blocks of cases which included: 4 new blocks for 60 cases of PTC and 2 blocks for benign thyroid lesions cases each block contained 30 cores (two cores of 1.5mm form each case) and one block for 10 cases of normal thyroid tissue contained 20 cores. H&E and immunohistochemistry staining by CD56, emerin, thyroglobulin and TTF-1 were performed.
In present work , 90 studied cases included 30 cases of benign thyroid lesions [6 cases (20%) of goiter, 6 cases (20%) of diffuse hyperplasia, 8cases (27%) of Hashimoto‟s thyroiditis and 10 cases (33%) of follicular adenoma} and 60 cases of papillary thyroid cancer {40 cases (66.7%) of classical papillary thyroid carcinoma, 15 cases (25%) of follicular variant of papillary thyroid carcinoma and 5 cases (8.3%) of papillary thyroid microcarcinoma].
Patients’ ages ranged from 17-59 years with a mean of age 39.32 ± 10.99 years. Seventy seven (85.5%) cases were female and thirteen (14.5%) cases were male & the size of the tumor was ranging from 0.5 to 5 cm with mean± SD of 2.85 ± 1.04cm.
Tissue microarray of 10 control cases (normal thyroid tissue) showed strong cytoplasmic expression of thyroglobulin (TG) in all cases (100%). Strong nuclear staining of thyroid transcription factor -1(TTF-1) was seen in 5 cases (50%), moderate staining in 3 cases (30%) and only 2 cases (20%) showed weak expression. On the other hand, one case (10%) showed moderate positive cytoplasmic membranous expression to CD56 immunostaining, 1 case (10%) showed weak expression, while 8 cases (80%) were negatively stained. Also, all normal tissue cases (100%) showed positive nuclear membrane highlight emerin expression, which included 4 cases (40%) were strongly stained, 4 cases (40%) were moderately stained and only 2 cases (20%) showed weak staining.
Summary and Conclusion
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Thyroglobulin positivity expression was seen in all studied cases (100%). There was no statistical significant correlation between thyroglobulin immunohistochemical expression in PTC & BTLs cases. While TTF-1 expression was seen in twenty eight (93.3%) out of BTLs cases, whereas two (6.7%) cases were negatively expressed. from sixty cases of PTC fifty seven (95%) cases were positive expressed, while only three (5%) cases were negatively expressed. No statistical significant association between TTF-1 expression in PTC & BTLs cases.
Findings of present study showed that CD56 loss cytoplasmic membranous expression demonstrated in fifty three (88.3%) out of sixty PTC cases and positively expressed only in seven (11.7%) cases. While positive expression showed in thirteen (43.3%) out of thirty cases of BTLs versus seventeen (56.7%) cases were negatively stained with highly significant association between immunohistochemical expression of CD56 in PTC & BTLs.
Furthermore, CD56 was positively expressed in thirteen (43.3%) out thirty cases of BTLs which included nine FA cases (eight strong and one moderately stained) and 4 cases HT (two moderate and two weak expression).Whereas, CD56 was negatively expressed in seventeen (56.7%) cases of BTLs which included all cases of DH and goiter, four cases of HT and only one case of FA. A highly statistical significant association was found between CD56 expression and types of BTLs. On the other hand , thirty four (85%) cases of CPTC showed negative CD56 staining, while six (15%) cases showed positive staining (moderate staining in 1case and weak staining in 5 cases). Fourteen (93.3%) out fifteen cases of FVPTC showed negative CD56 expression, whereas only one (6.7%) case was moderately positive stained. As well as all five (100%) cases of PTMC were negatively stained. There was no statistical significant association between variants of PTC and CD56 expression.
Moreover, the present results revealed that CD56 expression was negatively correlated with different clinical parameters in BTLs and PTC cases.
In present work assessment of emerin IHC expression for differenation of PTC versus BTLs was focused on two aspects:
a) Positivity expression of emerin staining. b) emerin highlighted nuclear alterations in PTC versus BTLs & comparison with HE stain.
The present result noticed that positive nuclear membrane highlight emerin staining showed in fifty two (86.7%) cases of PTC, while emerin was negatively expressed in eight (13.3%) cases of PTC. On the other hand, only three (10%) cases of BTLs were positively stained, whereas negatively stained in twenty seven (90%). A highly statistical significant relationship was between emerin expression in PTC and BTLs.
Emerin was negatively expressed in twenty seven (90%) out of thirty BTLs cases, which included all cases of FA, six cases of HT, all cases of DH and five cases of goiter. On the other hand, emerin positive staining showed only in three (10%) cases of BTLs, they included two cases of HT and only one case of goiter .There was no significant correlation between emerin expression & BTLs types.
Furthermore, the present work observed that thirty six cases of CPTC were positively emerin expressed ( 26 cases showed moderate expression, 7 cases showed weak positive ,
Summary and Conclusion
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3 cases were strongly expressed and only 4 cases of CPTC showed negative expression). On the other hand, 13 cases of FVPTC showed positive staining which included moderate staining in 9 cases, strong staining in 3 cases, one case showed weak staining and negatively stained in two cases. Also 3 cases of PTMC were positively stained (moderate staining only in 1 case, weak staining in 2 cases and only 2 cases of PTMC were negatively stained). No significant differences between variants of PTC and emerin expression.
Moreover, results revealed that emerin was negatively correlated with different clinical parameters in BTLs and PTC cases.
The sensitivity of CD56 as a negative marker for PTC and differentiated PTC from BTLs was high (88%), specificity was low (57%) as well as positive predictive value (PPV) was (80%), negative predictive value (NPV) was(71%), diagnostic accuracy (DA) was (78%). Therefore, CD56 could be a negative maker for diagnosis of PTC but not specific for differentiated PTC from BTLs. On the other hand, emerin as positive marker had high sensitivity (86%), specificity (90%), positive predictive value (97%) ,negative predictive value (77%) & diagnostic accuracy (88%).Thus emerin could be a good positive marker for diagnosis of PTC and highly specific for differentiated PTC from BTLs.
Otherwise, the obtained results showed that, nuclear membrane alterations as, garland, star like shape, crescent, predominantly nuclear oval shape, grooves, pseudo-inclusions, and nuclear protrusions with both H&E and emerin IHC were significantly more frequent in PTC than BTLs. Recognition of nuclear alterations by emerin IHC and H&E were better than with H&E alone.
In addition, comparison between emerin IHC and H&E in detection of nuclear alterations for diagnosis of PTC, garland like shape had the best diagnostic efficacy (91%) with emerin IHC than diagnostic efficacy (68.9%) of H&E. Star like shape, crescent, predominately oval nuclear shape and nuclear protrusions showed a good diagnostic efficacy(78.9%, 82.2%, 84%&76.7% respictively) with emerin compered to diagnostic efficacy H&E (68.9%,72.7%,80% & 56.6% respectively). On the other hand grooves had best diagnostic efficacy with H&E (96.7%) than emerin IHC (90%).