الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Wound healing may be complicated by excessive scarring, which has unpleasant physical, psychological and social consequences. Scars may be keloids, hypertrophic or atrophic scars. Keloids are excessive scars that grow beyond the boundaries of the original wound. They do not spontaneously regress and frequently recur after being excised. They usually result from surgery, trauma, burn injuries or extensive soft tissue trauma. Hypertrophic scars stay within the boundaries of the original lesion and may spontaneously regress with time. Hypertrophic scars can be classified as linear or widespread.
Discoidin domain receptors (DDRs); DDR1 and DDR2, lie at the intersection of two large receptor families, namely the extracellular matrix and tyrosine kinase receptors. DDR1 promotes inflammation in atherosclerosis, lung fibrosis and kidney injury, while DDR2 contributes to osteoarthritis. DDRs play an important role in modulating collagen synthesis and organization during scar formation. As collagen directly bound to the receptor ectodomain results in phosphorylation of the tyrosine kinase domain, which in turn leads to a downstream cascade signaling activity, so expression of collagen and DDRs may determine the nature and extent of tissue scarring.
Scarce number of studies studied the relation between DDR1 and scar.
This study aimed to investigate the role of DDR1 in pathogenesis and formation of scar through its immunohistochemical expression in lesional and perilesional skin of scar and to correlate its expression with the clinical and histopathological parameters.
In this study, data of 80 participants (40 patients with keloid and hypertrophic scars and 40 age, gender and site matched healthy subjects as a control group) were statistical analyzed.
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The mean age of the selected cases was 22.98±8.86 years, the median was 22 and range was 7-40 year. Males were 12 (30%) of cases and 28 (70%) were females, with1: 2.33 as male to female ratio. Positive family history of scar was found in 9 (22.5%) of cases. The mean value of duration of the disease was 17.53±8.5 years. Progressive course was in 21 (52.5%) of cases while Stationary course was in 19 (47.5%). Onset was rapid in 4 (10%) and gradual in 36 (90%) of cases. Clinical assessment of scars was done by Manchester scale, Total score ranged from 12 to 18 with a mean±SD 14.67±1.70 and median 15. Vancouver scale, Total score ranged from 6 to 13 with a mean±SD 9.90±2.17 and median 10.5. Stony brook scale, Total score ranged from 1 to 4 with a mean±SD 2.37±0.63 and median 2. There was no significant difference between case and control groups regarding age, gender.
There was significant difference between studied groups regarding family history and course of disease. Forty five percent of keloid cases had positive family history while all hypertrophic cases had negative family history. All keloid cases had progressive course whereas all hypertrophic cases had stationary course. A significant difference between studied groups was noted regarding Manchester, Vancouver and Stony brook scales (P>0.001 for all).
Regarding epidermal DDR1 expression; There were highly significant differences between cases and control groups regarding topography, intensity and H score values (P: <0.001). In normal skin; DDR1 was positively expressed with cytoplasmic locilization in all cases in epidermis. A significant stepwise decrease was noted in epidermal H-scores of DDR1 in peri-lesional skin of scar group, control and lesional skin of scar group (140, 60, and 30 respectively) (P: >0.001). In perilesional skin epidermis; DDR1 was positively expressed in all perilesional skin epidermis. Pattern was cytoplasmic in all cases. Regarding intensity, mild expression was
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present in 30% of the sections and 70% had moderate expression. H score ranged from 40 -180 with mean ±SD of 119.50 ± 47.61. In lesional skin epidermis; DDR1 was positively expressed in all lesional skin epidermis. Pattern was cytoplasmic in all cases. Regarding intensity, mild expression was present in all sections. H score ranged from 20 -40 with mean ±SD of 27.5 ± 8.09.
Regarding dermal DDR1 expression; There were highly significant difference between cases and control groups regarding status, intensity and H score values (P: <0.001). In normal skin; DDR1 was positively expressed with cytoplasmic localization in all cases in dermis. A significant stepwise decrease was noted in dermal H-scores of DDR1 in peri-lesional skin of scar group, control and lesional skin of scar group (130, 85, and 40 respectively) (P: >0.001). In perilesional skin dermis; DDR 1 was positively expressed in all perilesional skin epidermis. With cytoplasmic localization in all cases. Regarding intensity, mild expression was found in 40% of the sections, 40% had moderate expression and 20% had strong expression. H score ranged from 50 -220 with mean ±SD of 117.75 ± 54.61. In Lesional skin dermis; DDR 1 was positively expressed in 27.5% of lesional skin dermis while 72.5% were negative. Cytoplasmic localization was found in all cases. Mild intensity was found in all cases H score ranged from 30 -50 with mean ±SD of 38.5 ± 8.02.
Regarding epidermal and dermal expression of DDR1 in perilesional skin of keloid and hypertrophic scar cases and control group; A significant stepwise decrease was noted in epidermal H-score of DDR1 in peri-lesional skin of keloid, peri-lesional skin of hypertrophic and control groups (140, 125, 60 respectively) (P: >0.001).A significant stepwise decrease was noted in dermal H-score of DDR1 in peri-lesional skin of keloid, peri-lesional skin of hypertrophic and control groups (130, 125, 85 respectively) (P= 0.005).
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Regarding epidermal and dermal expression of DDR1 in lesional skin of keloid and hypertrophic scar cases and control group;
In epidermis; A significant difference between the studied groups was noted regarding epidermal expression intensity of DDR1, intensity was mild in all lesional skin of keloid and hypertrophic cases, while 52.5% of control group was mild (P: >0.001).A significant stepwise increase was noted in epidermal H-score of DDR1 in lesional skin of keloid, lesional skin of hypertrophic and control groups (25, 30, 60 respectively) (P: >0.001).
In dermis; A significant difference between the studied groups was noted regarding dermal expression status of DDR1, it was positive in 30% of lesional skin of keloid group, 25% of lesional skin of hypertrophic cases and 100% of control group (P: >0.001). A significant difference between the studied groups was noted regarding dermal expression intensity of DDR1, intensity was mild in all lesional skin of keloid and hypertrophic cases, while 50% of control group was mild (P: >0.001). A significant stepwise increase was noted in dermal H-score of DDR1 in lesional skin of keloid, lesional skin of hypertrophic cases and control groups (40, 40, 85 respectively) (P: >0.001).
Regarding epidermal and dermal expression of DDR1 in lesional and peri-lesional skin of keloid cases and control group; It was found that a significant difference between lesional skin and peri-lesional skin of keloid scar cases regarding topography of DDR1 (P=0.008). Significant differences between lesional skin and peri-lesional skin of keloid scar cases were found regarding DDR1 expression intensity in epidermis and dermis (P: >0.001 for both). Significant differences between lesional skin and peri-lesional skin of keloid scar cases were found regarding DDR1 expression H-score values in epidermis and dermis (P: >0.001 for both). A significant difference between lesional skin and peri-lesional skin of keloid scar cases was found regarding DDR1 dermal expression status (P: >0.001).
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Regarding epidermal and dermal expression of DDR1 in lesional and peri-lesional skin of hypertrophic scar cases and control group; It was found that a significant difference between lesional skin and peri-lesional skin of hypertrophic scar cases regarding epidermal topography of DDR1 (P= 0.008). Significant differences between lesional skin and peri-lesional skin of hypertrophic scar cases were found regarding DDR1 expression intensity in epidermis and dermis (P: >0.001 for both). Significant differences between lesional skin and peri-lesional skin of hypertrophic scar cases were found regarding DDR1 expression H-score values in epidermis and dermis (P: >0.001 for both). A significant difference between lesional skin and peri-lesional skin of hypertrophic scar cases was found regarding DDR1 dermal expression status (P: >0.001).
Also, we detected; A significant positive correlation between age of scar groups and lesional dermal H-score of DDR1 (r=0.391; P= 0.013). A significant positive correlation was found between duration of scar and lesional epidermal H-score of DDR1in scar group (r=0.362; P=0.022).
Regarding clinical assessment scales; A significant positive correlation was found between Vancouver clinical scale assessment and DDR1 dermal H-score in keloid scar (r=0.624; P=0.003). A significant positive correlation was found between Stony brook clinical scale assessment and DDR1 epidermal H-score in hypertrophic scar (r=0.508; P=0.022).
There was a significant positive correlation between lesional epidermal and lesional dermal H-score of DDR1 in keloid scar group (r=0.552; P=0.012).