Purchase this article with an account.
Ana Beatriz Toledo Dias, Pablo Zoroquiain, Dominique Fausto souza, Dana Faingold, Patrick T Logan, Miguel N Burnier; HSP90 expression is a useful tool for the differential diagnosis of ocular surface squamous neoplasia.. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3420.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
HSP90 is a chaperone protein that stabilizes and activates client proteins involved in malignant transformation. HSP90 is overexpressed in many malignant tumors, including squamous cell carcinomas of the head and neck. The aim of this study is to evaluate HSP90 expression in ocular surface squamous neoplasia (OSSN) and to assess its diagnostic value for the different lesions of the OSSN spectrum.
Seventy conjunctival squamous lesions, including 19 papillomas (Pa), 22 conjunctival intraepithelial neoplasia (CIN) I, 11 CIN II, 6 CIN III, and 12 squamous carcinoma (sqCA), were evaluated using automated immunohistochemical staining against HSP-90. As controls, 15 normal conjunctiva specimens were used. The staining was scored by evaluating staining intensity (0-3) and extent (0-4) and these values were multiplied to generate an immunoreactive score (IRS; 0-12). This process was performed for nuclear (nIRS) and cytoplasmic (cIRS) HSP90 staining. Also, intra-epithelium staining was evaluated as a percentage of total thickness (PTE).
All OSSN and 90% of controls were positive for HSP90; however, mean benign and malignant OSSN IRS were significantly higher than normal conjunctiva (P<0.0001). With respect to OSSN, cIRS had a higher HSP90 IRS in high grade compared to low grade lesions (Pa and CIN I; P<0.001). nIRS was significantly different between high grade lesions (CIN II vs CIN III-sqCA; P=0.0162). A cIRS >6 correlated with a high grade lesion (sensitivity [S] 58.3%, specificity [Sp] 97.4%), while a cIRS <4 correlated with a low grade lesion (S 43.6%, Sp 100%). An nIRS >6 in high grade lesions correlated with CIN III-sqCA (S 55.6%, Sp 81.8%), while an nIRS <4 correlated with CINII (S 45.5%, Sp 94.4%). PTE staining of <73% differentiated between CIN III and sqCA with an S of 91.7% and Sp of 100% for sqCA. nIRS, cIRS, and cIRS + nIRS did not correlate with the depth of infiltration or sqCA differentiation degree.
To the best of our knowledge, this is the first study using HSP90 as a marker to differentiate between benign, premalignant, and malignant lesions of the conjunctiva. The expression of HSP90 is particularly useful to differentiate low from high grade CIN and invasive sqCA of the conjunctiva. HSP90 may play an important role in stabilizing and activating client proteins involved in this malignant transformation.
This PDF is available to Subscribers Only