COX-2

a3 b3 c3 d3 C

a4 b4 c4 d4

a1 b1 c1 d1

Fig.5

Figure 1

Histopathological findings of papilloma (a: without candidiasis, b: with candidiasis) and verrucous hyperplasia (c: without candidiasis, d: with candidiasis). “C” means

candidiasis in the figures.

Papillary and verrucous outward proliferation with parakeratotic stratified squamous epithelium was observed in papilloma (Fig.1-a) and verrucous hyperplasia (Fig.1-c), respectively.

Pseudohyphae or hyphae penetrated vertically into the keratinized layer or upper layer of the prickle layer of papilloma with candidiasis (Fig.1-b).

Neutrophilic infiltration was observed in the connective tissue and was invaded in the epithelial tissue (Fig.1-d). PAS reaction revealed clearly hyphal invasion (inset in Fig.1-b and Fig.1-d).

Figure 2

Longitudinal section of Candidal hyphe (HL) was existed within the oral epithelium (E). Cross section of Candidal hyphe (HC) internalized into the epithelial cell inside a cytoplasmic vacuole (V).The cell covered with plasma membrane (PM) is surrounded by thick cell wall (CW). (Fig.2-1:x5,000).

Candial hypha containing mitochondrias (M) and a nuclear (N) had invaded along an intercellular bridge was observed. Desmosomal cell junction (D) of the epithelial cells (E) and dense tonofilament (TF) were arranged irregularly in the host cytoplasm. Destruction of desmosomal cell junction (arrow) and deficit of tonofilament (arrowhead) were also observed at the tip of the hypha

(Fig.2-2:x10,000).“C” means candidiasis in the figures.

Figure 3

In the without candidiasis group, a strong positive reaction was seen across the whole of the prickle layer, which presented a clearly scalar appearance (Figs.3-a,c).

In the candidiasis group, weaker expression was seen in the prickle layer (Figs.3-b (1),d(1)). Strong positive E-cadherin reaction was seen along the insertion sites of the hyphae (Figs.1-b(2),d(2), arrowhead). “C” means candidiasis in the figures.

Figure 4

CK13 was negative in the basal layer of papilloma and verrucous hyperplasia without candidiasis (Figs.4-a1,c1). In papilloma and verrucous hyperplasia with candidiasis, weakly positive in the basal layer and strongly positive in the whole

prickle layer. (Figs.4-b1,d1).

EGFR was almost negative in without candidiasis groups (Figs.4-a2,b2,c2,d2).

Weakly positive EGFR reactions were observed in the upper layer of the prickle layer in papilloma and verrucous hyperplasia with candidiasis (Figs.4-b2,d2).

Higher values for Ki-67 positivity were found in both the basal layer and the prickle layer of the candidiasis group (Figs.4-b3,d3) than the without candidiasis group (Figs.4-a3,c3). “C” means candidiasis in the figures.

Figure 5

NE and CD68 were almost completely negative the without candidiasis group (Figs.5-a1,c1,a2,c2). In papilloma and verrucous hyperplasia with candidiasis, strongly positive reactions were seen on the prickle layer and connective tissue (Figs.5-b1,d1,b2,d2).

COX-2 was negative in the without candidiasis group (Figs.5-a3,c3). In the candidiasis group, COX-2 was positive in all layers in papilloma (Fig.5-b3), and mix of strongly and weakly positive reaction was seen in verrucous hyperplasia (Fig.5-d3).

In the investigation of new blood vessels using CD105 (Figs.5-a4,b4,c4,d4),

numerous enlarged blood vessels were found in the connective tissue immediately below the basal membrane in papilloma (Fig.5-b4) and verrucous hyperplasia with candidiasis (Fig.5-d4). “C” means candidiasis in the figures.

㻼㼍㼠㼔㼛㼘㼛㼓㼕㼏㼍㼘㻌㻰㼕㼍㼓㼚㼛㼟㼕㼟㻌㻌㻔㻭㼢㼑㼞㼍㼓㼑㻌㼍㼓㼑㻌㼼㻿㻚㻰㻚㻕 㻭㼓㼑 㻿㼑㼤 㻸㼛㼏㼍㼠㼕㼛㼚

㻺㼛㼞㼙㼍㼘㻌㼛㼞㼍㼘㻌㼙㼡㼏㼛㼟㼍 㻞㻞 㻲 㻳㼕㼚㼓㼕㼢㼍

㻟㻞 㻲 㻳㼕㼚㼓㼕㼢㼍

㻝㻝 㻹 㼀㼛㼚㼓㼡㼑

㻞㻢 㻲 㻳㼕㼚㼓㼕㼢㼍

㻟㻥 㻹 㻳㼕㼚㼓㼕㼢㼍

㻼㼍㼜㼕㼘㼘㼛㼙㼍㻌㼣㼕㼠㼔㼛㼡㼠㻌㻯㼍㼚㼐㼕㼐㼕㼍㼟㼕㼟㻌㻔㻠㻢㻚㻟㼼㻝㻢㻚㻡㻕 㻡㻜 㻹 㻼㼍㼘㼍㼠㼑

㻡㻜 㻹 㻼㼍㼘㼍㼠㼑

㻞㻡 㻲 㻳㼕㼚㼓㼕㼢㼍

㻞㻡 㻲 㻳㼕㼚㼓㼕㼢㼍

㻡㻠 㻲 㼀㼛㼚㼓㼡㼑

㻠㻞 㻲 㼀㼛㼚㼓㼡㼑

㻣㻝 㻹 㼀㼛㼚㼓㼡㼑

㻡㻠 㻲 㼀㼛㼚㼓㼡㼑

㻼㼍㼜㼕㼘㼘㼛㼙㼍㻌㼣㼕㼠㼔㻌㻯㼍㼚㼐㼕㼐㼕㼍㼟㼕㼟㻌㻔㻡㻠㻚㻜㼼㻞㻜㻚㻜㻕 㻡㻡 㻲 㻸㼕㼜

㻡㻥 㻲 㻼㼍㼘㼍㼠㼑

㻞㻤 㻲 㻼㼍㼘㼍㼠㼑

㻢㻠 㻲 㼀㼛㼚㼓㼡㼑

㻤㻠 㻹 㼀㼛㼚㼓㼡㼑

㻢㻥 㻲 㼀㼛㼚㼓㼡㼑

㻞㻡 㻲 㼀㼛㼚㼓㼡㼑

㻠㻤 㻹 㼀㼛㼚㼓㼡㼑

㼂㼑㼞㼞㼡㼏㼛㼡㼟㻌㼔㼥㼜㼑㼞㼜㼘㼍㼟㼕㼍㻌㼣㼕㼠㼔㼛㼡㼠㻌㻯㼍㼚㼐㼕㼐㼕㼍㼟㼕㼟㻌㻔㻡㻤㻚㻟㼼㻝㻠㻚㻤㻕 㻠㻜 㻹 㻼㼍㼘㼍㼠㼑

㻡㻥 㻲 㻼㼍㼘㼍㼠㼑

㻣㻞 㻲 㻳㼕㼚㼓㼕㼢㼍

㻣㻜 㻹 㻳㼕㼚㼓㼕㼢㼍

㻢㻢 㻲 㻳㼕㼚㼓㼕㼢㼍

㻢㻢 㻲 㻳㼕㼚㼓㼕㼢㼍

㻟㻡 㻹 㼀㼛㼚㼓㼡㼑

㼂㼑㼞㼞㼡㼏㼛㼡㼟㻌㼔㼥㼜㼑㼞㼜㼘㼍㼟㼕㼍㻌㼣㼕㼠㼔㻌㻯㼍㼚㼐㼕㼐㼕㼍㼟㼕㼟㻌㻔㻢㻥㻚㻞㼼㻞㻚㻣㻕 㻢㻤 㻹 㻼㼍㼘㼍㼠㼑

㻣㻝 㻹 㻼㼍㼘㼍㼠㼑

㻢㻡 㻹 㼀㼛㼚㼓㼡㼑

㻣㻝 㻲 㼀㼛㼚㼓㼡㼑

㻣㻝 㻹 㼀㼛㼚㼓㼡㼑

㻹㻌㻦㻌㻹㼍㼘㼑 㻲㻌㻦㻌㻲㼑㼙㼍㼘㼑

㻿㻚㻰㻚㻌㻦㻌㻿㼠㼍㼚㼐㼍㼞㼐㻌㻰㼑㼢㼕㼍㼠㼕㼛㼚

㼀

㼀㼍㼎㼘㼑㻌㻝㻌㻿㼡㼎㼖㼑㼏㼠㼟㻌㼛㼒㻌㼕㼙㼙㼡㼚㼛㼔㼕㼟㼠㼛㼏㼔㼑㼙㼕㼏㼍㼘㻌㼟㼠㼡㼐㼥

㻼㼍㼞㼜㼛㼟㼑 㻭㼚㼠㼕㼎㼛㼐㼥 㻯㼘㼛㼚㼑 㻰㼕㼘㼡㼠㼕㼛㼚 㻯㼛㼙㼜㼍㼚㼥 㻾㼑㼠㼞㼕㼑㼢㼍㼘㻌㼙㼑㼠㼔㼛㼐㼟 㻝㻕㻌㻯㼑㼘㼘㻌㼍㼐㼔㼑㼟㼕㼛㼚

㻱㻙㻯㼍㼐㼔㼑㼞㼕㼚 㻺㻴㻯㻙㻟㻤 㻝㻦㻝㻜㻜 㻰㼍㼗㼛㻯㼥㼠㼛㼙㼍㼠㼕㼛㼚 㻴㼑㼍㼠㻌㻝㻞㻝䉝㻘㻌㻌㻡㼙㼕㼚

㻞㻕㻌㻯㼥㼠㼛㼗㼑㼞㼍㼠㼕㼚

㻯㼥㼠㼛㼗㼑㼞㼍㼠㼕㼚㻌㻔㻯㻷㻝㻟㻕 㻰㻱㻙㻷㻝㻟 㻝㻦㻠㻡㻜 㻰㼍㼗㼛㻯㼥㼠㼛㼙㼍㼠㼕㼛㼚 㻹㼕㼏㼞㼛㼣㼍㼢㼑㻘㻌㻌㻝㻡㼙㼕㼚

㻟㻕㻌㻼㼞㼛㼘㼕㼒㼑㼞㼍㼠㼕㼢㼑㻌㼒㼍㼏㼠㼛㼞

㻱㻳㻲㻾㻘㻌㼃㼕㼘㼐㻙㼀㼥㼜㼑 㻰㼍㼗㻙㻴㻝㻙㼃㼀 㻝㻦㻞㻜㻜 㻰㼍㼗㼛㻯㼥㼠㼛㼙㼍㼠㼕㼛㼚 㻴㼑㼍㼠㻌㻝㻞㻝䉝㻘㻌㻌㻡㼙㼕㼚

㻷㼕㻙㻢㻣㻌㻭㼚㼠㼕㼓㼑㼚 㻹㻵㻮㻙㻝 㻝㻦㻝㻜㻜 㻰㼍㼗㼛㻯㼥㼠㼛㼙㼍㼠㼕㼛㼚 㻴㼑㼍㼠㻌㻝㻞㻝䉝㻘㻌㻌㻡㼙㼕㼚

㻠㻕㻌㻵㼚㼒㼘㼍㼙㼙㼍㼠㼛㼞㼥㻌㼞㼑㼟㼜㼛㼚㼟㼑

㻺㼑㼡㼠㼞㼛㼜㼔㼕㼘㻌㻱㼘㼍㼟㼠㼍㼟㼑㻌㻔㻺㻱㻕 㻺㻼㻙㻡㻣 㻝㻦㻝㻜㻜 㻰㼍㼗㼛㻯㼥㼠㼛㼙㼍㼠㼕㼛㼚 㻙

㻯㻰㻢㻤 㻷㻼㻝 㻝㻦㻝㻜㻜 㻰㼍㼗㼛㻯㼥㼠㼛㼙㼍㼠㼕㼛㼚 㻼㼞㼛㼠㼑㼕㼚㼍㼟㼑㻌㻷㻘㻌㻡㼙㼕㼚

㻯㻻㼄㻙㻞 㻯㼄㻙㻞㻥㻠 㻝㻦㻝㻜㻜 㻰㼍㼗㼛㻯㼥㼠㼛㼙㼍㼠㼕㼛㼚 㻹㼕㼏㼞㼛㼣㼍㼢㼑㻘㻌㻌㻝㻡㼙㼕㼚

㻯㻰㻝㻜㻡 㻿㻴㻢㼔 㻝㻦㻠㻝㻜 㻰㼍㼗㼛㻯㼥㼠㼛㼙㼍㼠㼕㼛㼚 㻼㼞㼛㼠㼑㼕㼚㼍㼟㼑㻌㻷㻘㻌㻡㼙㼕㼚

㼀

㼀㼍㼎㼘㼑㻌㻞㻌㻭㼚㼠㼕㼎㼛㼐㼕㼑㼟㻌㼍㼚㼐㻌㼞㼑㼠㼞㼕㼑㼢㼍㼘㻌㼙㼑㼠㼔㼛㼐㼟㻌㼡㼟㼑㼐㻌㼕㼚㻌㼠㼔㼑㻌㼜㼞㼑㼟㼑㼚㼠㻌㼟㼠㼡㼐㼥

㻹㻵 㻮㼍㼟㼍㼘 㻼㼞㼕㼏㼗㼘㼑

㻯㼍㼟㼑 㻺㼛㻚 㻵㼚㼒㼘㼍㼙㼙㼍㼠㼕㼛㼚 㻭㼢㼑㻚㼼㻿㻰 㻮㼍㼟㼍㼘 㻸㼛㼣㼑㼞 㼁㼜㼜㼑㼞 㻷㼑㼞㼍㼠㼕㼚㼕㼦㼑㼐 㻮㼍㼟㼍㼘 㻸㼛㼣㼑㼞 㼁㼜㼜㼑㼞 㻭㼢㼑㻚㼼㻿㻰 㻭㼢㼑㻚㼼㻿㻰 㻮㼍㼟㼍㼘 㻸㼛㼣㼑㼞 㼁㼜㼜㼑㼞

㻺㼛㼞㼙㼍㼘㻌㼛㼞㼍㼘㻌㼙㼡㼏㼛㼟㼍 㻡 㼚㼛㼚㼑㻌㼠㼛㻌㼟㼘㼕㼓㼔㼠㼘㼥 㻜㻚㻞㼼㻜㻚㻡 䠇䡚㼼 䠇 㼼䡚䠇 㻙 㻙 㼼䡚䠇 䠇 㻠㻚㻣㼼㻜㻚㻡 㻜㻚㻝㼼㻜㻚㻝 㻙 㻙 㻙

㻼㼍㼜㼕㼘㼘㼛㼙㼍

㼣㼕㼠㼔㼛㼡㼠㻌㼏㼍㼚㼐㼕㼐㼕㼍㼟㼕㼟 㻤 㼚㼛㼚㼑㻌㼠㼛㻌㼟㼘㼕㼓㼔㼠㼘㼥 㻜㻚㻢㼼㻜㻚㻞 䠇 䠇䠇 䠇䠇䡚䠇 㻙 㻙 䠇䡚䠇䠇 䠇䡚䠇䠇 㻞㻢㻚㻝㼼㻝㻜㻚㻥 㻜㻚㻟㼼㻜㻚㻡 㻙 㻙㻌䡚㼼 㻙㻌䡚㼼

㻼㼍㼜㼕㼘㼘㼛㼙㼍

㼣㼕㼠㼔㻌㼏㼍㼚㼐㼕㼐㼕㼍㼟㼕㼟 㻤 㼙㼕㼘㼐㻌㼠㼛㻌㼙㼛㼐㼑㼞㼍㼠㼑 㻝㻚㻠㼼㻜㻚㻜 䠇䡚㼼 䠇䡚㼼 㼼䡚䠉 䠇 㼼 㼼䡚䠇 䠇䡚㼼 㻞㻤㻚㻡㼼㻝㻠㻚㻟 㻜㻚㻟㼼㻜㻚㻣 㻙 㻙㻌䡚㼼 㼼䡚䠇

㼂㼑㼞㼞㼡㼏㼛㼡㼟㻌㼔㼥㼜㼑㼞㼜㼘㼍㼟㼕㼍

㼣㼕㼠㼔㼛㼡㼠㻌㼏㼍㼚㼐㼕㼐㼕㼐㼍㼟㼕㼟 㻣 㼚㼛㼚㼑㻌㼠㼛㻌㼟㼘㼕㼓㼔㼠㼘㼥 㻜㻚㻡㼼㻜㻚㻟 䠇 䠇䠇 䠇䠇䡚䠇 㻙 㻙 䠇䡚䠇䠇 䠇䡚䠇䠇 㻝㻞㻚㻝㼼㻝㻟㻚㻥 㻜㻚㻝㼼㻜㻚㻝 㻙 㻙㻌䡚㼼 㻙㻌䡚㼼

㼂㼑㼞㼞㼡㼏㼛㼡㼟㻌㼔㼥㼜㼑㼞㼜㼘㼍㼟㼕㼍

㼣㼕㼠㼔㻌㼏㼍㼚㼐㼕㼐㼕㼍㼟㼕㼟 㻡 㼙㼕㼘㼐㻌㼠㼛㻌㼙㼛㼐㼑㼞㼍㼠㼑 㻜㻚㻣㼼㻜㻚㻠 䠇䡚㼼 䠇䡚㼼 㼼䡚䠉 䠇䠇 㼼 䠇䡚䠇䠇 㼼䡚䠇 㻟㻞㻚㻣㼼㻝㻠㻚㻠 㻜㻚㻣㼼㻞㻚㻞 㻙 㻙㻌䡚㼼 㼼䡚䠇

㻮㼍㼟㼍㼘㻌㻦㻌㻮㼍㼟㼍㼘㻌㼏㼑㼘㼘㻌㼘㼍㼥㼑㼞 㻼㼞㼕㼏㼗㼘㼑㻌㻦㻌㻼㼞㼕㼏㼗㼘㼑㻌㼏㼑㼘㼘㻌㼘㼍㼥㼑㼞 㻹㻵㻌㻦㻌㻹㼕㼠㼛㼟㼕㼟㻌㼕㼚㼐㼑㼤

㻼㻵㻌㻦㻌㻼㼞㼛㼘㼕㼒㼑㼞㼍㼠㼕㼢㼑㻌㼕㼚㼐㼑㼤

㻱㻙㼏㼍㼐㼔㼑㼞㼕㼚㻘㻌㻯㻷㻝㻟㻘㻌㼍㼚㼐㻌㻱㻳㻲㻾㻌㻦㻌䠇䠇㻌㻔㼟㼠㼞㼛㼚㼓㻌㼜㼛㼟㼕㼠㼕㼢㼑㻕㻘㻌䠇㻌㻔㼙㼛㼐㼑㼞㼍㼠㼑㻌㼜㼛㼟㼕㼠㼕㼢㼑㻕㻘㻌㼼㻌㻔㼣㼑㼍㼗㻌㼜㼛㼟㼕㼠㼕㼢㼑㻕㻘㻌㻙㻌㻔㼚㼑㼓㼍㼠㼕㼢㼑㻕 㻖㻌㻦㻌㻯㼔㼕㻙㼟㼝㼡㼍㼞㼑㻌㼠㼑㼟㼠㻘㻌㼜㻌㻨㻜㻚㻜㻜㻝

㼀

㼀㼍㼎㼘㼑㻌㻟㻌㻾㼑㼟㼡㼘㼠㼟㻌㼛㼒㻌㼔㼕㼟㼠㼛㼜㼍㼠㼔㼛㼘㼛㼓㼕㼏㼍㼘㻌㼍㼚㼐㻌㼕㼙㼙㼡㼚㼛㼔㼕㼟㼠㼛㼏㼔㼑㼙㼕㼏㼍㼘㻌㼟㼠㼍㼕㼚㼕㼚㼓㼟㻌

㻴㻚㻱㻚 㻯㻷㻝㻟 㻼㻵㻌㻔㻷㼕㻙㻢㻣㻕

㻼㼞㼕㼏㼗㼘㼑 㻱㻙㼏㼍㼐㼔㼑㼞㼕㼚

㻼㼞㼕㼏㼗㼘㼑

㻱㻳㻲㻾 㻼㼞㼕㼏㼗㼘㼑

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