الفهرس 
Material and MethodsOnly 14 pages are availabe for public view
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Abstract
Summary
This study aims first, at evaluation of diagnostic value of extent of expression of MMP-7, extent and pattern of expression of P-Cadherin, and morphometric measures (minimum and maximum nuclear diameter, MNA, MNEF) in different melanocytic tumors. Second, is to compare and correlate the findings with other clinicopathological variants such as, tumors size, Breslow thickness and Clark level of invasion. Statistical analysis and correlations were made for all these variants.
This retrospective study was carried upon 50 Egyptian patients with different melanocytic tumors during the years 2003-2009.The 50 melanocytic tumors included 24 cases of intradermal nevus, 6 cases of acral lentiginous melanoma (ALM), and 20 cases of nodular melanoma. The studied cases included 33 female (17 nevi cases, 16 cases of melanoma), and 17 male ( 7 cases of nevi, 10 cases of melanoma).the age of studied cases ranged from 7 ys up to 60 ys for nevi cases with mean age 37 years, and ranged from 20 ys up to 90 ys for melanoma cases with mean age 53.9 year.
Melanoma cases were classified according to Breslow thickness. All cases of ALM had a Breslow thickness ≤ 0.76mm. as regard 20 cases of nodular melanoma, 5 cases had Breslow thickness ≤ 0.76 mm, 10 cases had a thickness 0.76-1.5mm, and 5 cases had a thickness >1.5 mm. As regard Clark level of invasion in ALM, 3 cases were at level II, and 3 cases were at level III. Concerning NM cases, 9 cases were at level IV, and 11 cases were at level V.
Mitotic rate /5HPF were counted for different melanocytic tumors. In cases of nevi , 22 cases had mitotic rate <1/5HPF, 2 cases had mitotic rate one / 5HPF. All ALM cases had mitotic rate 1-4/5HPF. As regard NM cases, 10 cases had mitotic rate 1-4l5HPF, and 10 cases had mitotic rate >4/5HPF.
In the current study, morphometric analysis was carried out by means of Olympus soft imaging system to measure the minimum and maximum nuclear diameter, mean nuclear area. Both minimum and maximum nuclear diameters were used to calculate the mean nuclear elongation factor on routine H&E sections.
The mean nuclear area for all cases was 44.6 um2.All cases of nevi had MNA ≤ 44.6 um2. in ALM cases, one case had MNA ≤ 44.6 um2, and 5 cases had MNA > 44.6 um2. For NM cases, one case had MNA ≤ 44.6 um2 and 19 cases had MNA > 44.6 um2. There was a statistically highly significant positive correlation between MNA and histopathological type of Melanocytic tumors. Also a significant positive correlation between size of the tumor and MNA of melanocytic tumors was detected (P value : <0.05) as in nevi , cases with size > 0.6mm had a greater MNA than cases with a size ≤ 0.6mm (36.35 um2 vs 27.34 um2).
The MNEF for all the cases was 0.55. in nevi cases 9 cases had MNEF ≤ , and 15 cases had MNEF > 0.55. as regard Melanoma cases, 17 cases ( 4 cases of ALM, 13 NM cases) had MNEF ≤ 0.55 and 9 cases (2 cases of ALM, 7 cases of NM) had MNEF > 0.55. No statistically significant correlation between MNEF and histopathological type of melanocytic tumors was found, or between MNEF and other clinicopathological or immunohistochemical parameters. Though MNEF could not be reported as a reliable diagnostic factor for differentiation between different melanocytic tumors.
Extent of MMP-7 was detected by immunohistochemical staining technique. MMP-7 was detected as brown granular staining of melanocytic
cytoplasm. The criteria for scoring the stained sections ere: negative (negative or <10% of whole tumor mass stained), +1 (10-25% stained), +2 (25%-50% stained), and +3 (> 50% of whole tumor mass stained).
Among 24 cases of nevi, 7 cases (29.2%) showed (+1) expression, one case (4.2%) showed (+2) expression, and 16 cases (66.6%) showed (-ve) expression. In ALM one case (16.7%) showed (+1) expression, 2 cases (33.3%) showed (+2), and 3 cases (50%) showed (+3) expression . However in NM , 2 cases (10%) showed (+1) , 5 cases (25%) showed (+2),11 cases (55%)showed (+3) expression, and 2 cases (10%) showed (-ve) expression . a statically significant correlation between extent of MMP-7 expression and histopathological type of melanocytic tumors (P value < 0.05).
Statistically, there was a significant positive correlation between extent of MMP-7 expression and MNA in melanocytic tumors (P value < 0.05) as in nevi and melanoma cases there is progressive increase in MNA parallel to increased expression of MMP-7. Also, Statistically, there was a significant positive correlation between extent of MMP-7 expression and Clark level in malignant melanoma cases (P value : < 0.05).
Extent and pattern of expression of P-cadherin were detected by immunostaining technique. The melanocytic cell membrane and occasionally the cytoplasm were stained. Tumors presenting staining in < 10% were recorded as negative, while tumors presenting staining ≥ 10% were recorded as positive.
As regard extent of P-Cadherin, among 24 cases of nevus, 6 cases (25%) showed positive expression of P-Cadherin, and 18 cases (75%) showed negative expression of P-Cadherin. Among 6 cases of ALM, 5 cases (83.3%) showed positive expression and one case (16.7%) showed negative expression. However, among 20 cases of NM, 18 cases (90% ) showed positive expression of P-Cadherin and 2 cases (10%) showed negative expression of P-Cadherin. Statistically, there is a highly significant positive correlation between extent of P-Cadherin expression and histopathological type of melanocytic lesions (P value < 0.01).
As regard pattern of expression of P-cadherin, all 6 cases of nevi (100%) that showed positive expression of P-Cadherin showed membranous brown immunostaining of P-Cadherin. As regard malignant melanoma cases, all 5 cases of ALM (100%) showed membranous expression of P-Cadherin, however among 18 cases of NM melanoma that showed positive expression of P-Cadherin,, 6 cases (33.3%) showed membranous staining only, and 12 cases (66.7%) showed both membranous and cytoplasmic expression. Statistically, there is a highly significant positive correlation between pattern of P-Cadherin expression and histopathological type of melanocytic lesions (P value < 0.01).
Statistically, there is a highly significant positive correlation between extent of P-Cadherin expression and Clark level of invasion and Breslow thickness in malignant melanoma cases (P value : <0.01, <0.05 respectively) and also between extent of P-Cadherin expression and MNA of melanocytic tumors (P value : <0.01) as in nevi , cases with negative expression of P-Cadherin had MNA smaller than those with positive expression (29.4 μm2 vs 31.8 μm2). In melanoma, cases with negative expression had MNA 57.3 μm2 and cases with positive expression had MNA 59.9 μm2.
In the current study, a statistically high significant positive correlation between extent of P-Cadherin expression and mitotic count / 5HPF in melanocytic tumors (P value : <0.01). Also a significant positive correlation between extent of MMP-7 expression and extent of P-Cadherin expression in melanocytic tumors (P value : < 0.05) was reported as in nevi and melanoma cases with positive expression of P-Cadherin, there is progressive increase in the extent of expression of MMP-7.