Deficiency in infiltration of CD8/CD3 positive lymphocytes and macrophages plays a role in lip carcinogenesis: an immunohistochemical study

Magalhães, Iana Aragão; Costa, Gabriella Alves Juliao; Borges, Marcela Maria Fontes; Carlos, Anna Clara Aragão Matos; Mesquita, Karine Cestaro; Arruda, Larissa Mont´Alverne de; Cunha, Maria do Perpétuo Socorro Saldanha; Sousa, Fabrício Bitu; Silva, Paulo Goberlânio de Barros

doi:10.1016/j.bjorl.2023.101379

Acessibilidade / Reportar erro

Brasil

Brazilian Journal of Otorhinolaryngology

Español English

Brasil

Español English

sumário « anterior atual seguinte »

Sumário

Original article • Braz. j. otorhinolaryngol. 90 (2) • 2024 • https://doi.org/10.1016/j.bjorl.2023.101379 copy

Deficiency in infiltration of CD8/CD3 positive lymphocytes and macrophages plays a role in lip carcinogenesis: an immunohistochemical study

Authorship SCIMAGO INSTITUTIONS RANKINGS

Abstract

Objective

To evaluate the immunoexpression profile for CD8, CD3, CD20 and CD68 in the process and carcinogenesis of Carcinoma of the vermilion lip.

Methods

Average cell count with positive expression for CD3, CD8, CD20 and CD68. The CD8/CD3 ratio calculated in the region was based on the percentage of positive cells in a total of malignant cells. Kruska-Wallis/Dunn, Mann-Whitney and Spearman correlation tests (SPSS, p< 0.05) were used.

Results

In the Aquitic Cheilitis samples, there was an increase in intraepithelial CD8+ and CD68+. In LSCCs, there was an increase in peritumoral and intratumoral CD3+, CD8+, CD20+ and CD68+ cells. In peritumoral LSCC, CD3+ and CD8+ showed a direct correlation (p= 0.004), and CD68+ and CD8+ (p= 0.017). In the intraepithelial region, CD8+ correlated with CD20+ (p= 0.014) and CD68+ (p= 0.013). In the CAs, CD3 (p< 0.001) and CD8 (p= 0.025) correlated intraepithelial and subepithelial. In LSCC CD3+ (p= 0.002), CD8+ (p= 0.001) and CD68+ (p= 0.030) had intra and peritumoral correlation.

Conclusion

CD68+ is the first interacting cell with the greatest capacity to migrate to the tumor and interact with CD3, CD8 and CD20. Apparently, CD20 affects perineural invasion.

Level of evidence: Level 2.

Keywords
Lip neoplasms; Tumor microenvironment; Lymphocytes; Tumor-infiltrating

Highlights

Macrophages (CD68+) migrate into the tumor and interact with CD3, CD8 and CD20.

CD20 affects perineural invasion and histological gradation.

More aggressive tumors have lower amounts of CD20.

	CD3		CD8		CD20		CD68
	PT	IT	PT	IT	PT	IT	PT	IT
Lip lesions
Lip (n= 15)	129.5 ± 57.2	38.9 ± 23.2	26.8 ± 19.4	12.3 ± 7.8	5.1 ± 10.2	0.0 ± 0.0	54.9 ± 52.1	1.3 ± 4.0
Cheilitis (n= 30)	138.2 ± 124.8	21.1 ± 17.0	43.4 ± 36.5^c c p< 0.05 versus cheilitis (media ± SD).	14.6 ± 22.1	7.4 ± 15.8	0.0 ± 0.0	81.8 ± 69.1^c c p< 0.05 versus cheilitis (media ± SD).	0.9 ± 2.9
LSCC (n= 45)	212.8 ± 135.3^b b p< 0.05 versus lip. ,^c c p< 0.05 versus cheilitis (media ± SD).	67.3 ± 41.8 ^b b p< 0.05 versus lip. ,	128.5 ± 96.1^b b p< 0.05 versus lip. ,^c c p< 0.05 versus cheilitis (media ± SD).	48.2 ± 48.9^b b p< 0.05 versus lip. ,^c c p< 0.05 versus cheilitis (media ± SD).	85.7 ± 86.7^b b p< 0.05 versus lip. ,^c c p< 0.05 versus cheilitis (media ± SD).	9.4 ± 11.0^b b p< 0.05 versus lip. ,^c c p< 0.05 versus cheilitis (media ± SD).	31.1 ± 24.7^b b p< 0.05 versus lip. ,^c c p< 0.05 versus cheilitis (media ± SD).	53.9 ± 33.4^b b p< 0.05 versus lip. ,^c c p< 0.05 versus cheilitis (media ± SD).
p-value^a a Test Kruskal-Wallis/Dunn.	0.037	<0.001	<0.001	0.035	<0.001	<0.001	0.001	<0.001
Histological grading of dysplasias (Cheilitis)
Low risk (n= 19)	145.5 ± 136.9	24.1 ± 19.3	46.8 ± 42.7	18.9 ± 26.4	7.0 ± 17.3	0.0 ± 0.0	94.9 ± 78.0	0.4 ± 0.5
High risk (n= 11)	122.5 ± 103.1	14.7 ± 8.6	36.7 ± 21.1	6.0 ± 3.6	7.9 ± 15.1	0.0 ± 0.0	61.1 ± 50.8	1.7 ± 4.5
p-value^a a Test Kruskal-Wallis/Dunn.	0.721	0.275	0.596	0.366	0.914	1.000	0.327	0.372
Histological grading of LSCC
Low (n= 29)	233.4 ± 152.6	71.0 ± 45.6	142.7 ± 112.9	46.7 ± 42.1	90.5 ± 85.0	12.6 ± 11.6^b b p< 0.05 versus lip.	32.7 ± 30.2	52.2 ± 36.5
High (n= 17)	173.3 ± 96.6	62.4 ± 36.9	108.3 ± 56.7	53.2 ± 62.3	68.2 ± 88.9	3.8 ± 7.5	29.8 ± 8.1	57.3 ± 29.2
p-value^a a Test Kruskal-Wallis/Dunn.	0.179	0.532	0.314	0.705	0.460	0.019	0.755	0.675
Lymphovascular invasion (LSCC)
No (n= 40)	207.9 ± 138.9	68.8 ± 44.5	132.3 ± 103.0	50.1 ± 52.6	82.8 ± 82.2	10.6 ± 11.5	31.2 ± 26.6	54.8 ± 34.9
Yes (n= 5)	236.8 ± 130.3	59.4 ± 19.4	117.8 ± 49.3	41.8 ± 19.7	81.4 ± 117.9	2.4 ± 3.4	34.6 ± 8.8	48.6 ± 29.2
p-value^a a Test Kruskal-Wallis/Dunn.	0.663	0.645	0.762	0.732	0.973	0.126	0.781	0.709
Perineural invasion (LSCC)
No (n= 32)	220.1 ± 144.0	66.4 ± 42.9	130.5 ± 99.5	50.4 ± 55.8	92.2 ± 85.2	11.6 ± 12.0^c c p< 0.05 versus cheilitis (media ± SD).	31.4 ± 28.0	55.2 ± 35.1
Yes (n= 13)	190.3 ± 120.3	71.1 ± 42.2	129.5 ± 95.2	45.0 ± 27.0	56.8 ± 86.4	3.7 ± 4.6	32.4 ± 12.6	50.3 ± 31.7
p-value^a a Test Kruskal-Wallis/Dunn.	0.532	0.748	0.978	0.770	0.271	0.026	0.917	0.716

	CD3		CD8		CD20		CD68
	PT	IT	PT	IT	PT	IT	PT	IT
Sex
Female (n= 11)	192.3 ± 138.3	46.1 ± 30.8	98.6 ± 99.3	36.7 ± 45.3	55.3 ± 88.8	5.5 ± 11.6	63.3 ± 60.7	21.5 ± 31.5
Male (n= 34)	174.8 ± 124.6	52.9 ± 43.2	92.5 ± 85.0	38.6 ± 45.5	49.6 ± 71.2	5.1 ± 8.3	42.6 ± 43.7	34.5 ± 37.9
p-value^a a Mann-Whitney head.	0.594	0.498	0.807	0.886	0.780	0.889	0.120	0.177
Age
Up to 65 (n= 24)	175.2 ± 111.0	53.3 ± 42.9	105.8 ± 101.1	42.0 ± 43.4	59.1 ± 76.3	7.4 ± 10.8	42.5 ± 38.3	33.4 ± 35.1
>65 (n= 21)	186.2 ± 146.9	47.7 ± 35.7	82.4 ± 74.3	34.1 ± 47.0	44.3 ± 77.1	3.2 ± 7.5	56.0 ± 59.7	27.2 ± 37.6
p-value^a a Mann-Whitney head.	0.718	0.550	0.314	0.529	0.432	0.069	0.276	0.490
T
T1/2 (n= 30)	182.5 ± 117.3	52.3 ± 33.8	153.1 ± 116.1	63.3 ± 59.1	94.1 ± 78.4	15.5 ± 13.3	27.1 ± 17.7	46.9 ± 32.3
T3/4 (n= 15)	190.0 ± 142.5	70.2 ± 40.1	165.0 ± 162.3	36.4 ± 22.2	76.8 ± 108.8	11.4 ± 17.0	51.0 ± 48.9	53.4 ± 39.1
p-value^a a Mann-Whitney head.	0.915	0.379	0.872	0.350	0.728	0.615	0.181	0.737
N
N0 (n= 29)	203.3 ± 109.4	67.3 ± 35.7	179.8 ± 131.9	65.3 ± 61.6	117.3 ± 97.6	13.0 ± 12.6	24.1 ± 13.3	56.9 ± 34.0
N+ (n= 16)	148.3 ± 124.6	59.5 ± 46.5	123.0 ± 123.5	37.8 ± 23.3	44.8 ± 41.3	15.8 ± 17.3	51.5 ± 45.1	37.3 ± 31.8
p-value^a a Mann-Whitney head.	0.360	0.705	0.418	0.320	0.112	0.719	0.105	0.284
M
M0 (n= 47)	207.5 ± 128.7	67.3 ± 37.2	168.4 ± 133.1	66.2 ± 57.7	89.9 ± 82.1	16.8 ± 14.0	37.5 ± 37.5	54.4 ± 33.4
M1 (n= 3)	108.3 ± 67.1	48.0 ± 33.1	57.7 ± 28.4	35.0 ± 26.7	56.3 ± 39.3	7.7 ± 8.0	20.0 ± 14.5	23.3 ± 13.6
p-value^a a Mann-Whitney head.	0.235	0.439	0.192	0.394	0.517	0.313	0.457	0.154
Recurrence
No (n= 47)	221.2 ± 136.0	69.6 ± 41.8	131.6 ± 97.9	49.5 ± 50.4	88.3 ± 89.4	9.0 ± 10.5	30.9 ± 25.0	56.4 ± 33.4
Yes (n= 3)	104.7 ± 69.3	37.0 ± 35.0	94.0 ± 78.9	32.3 ± 25.7	54.3 ± 37.6	13.7 ± 18.0	33.0 ± 26.1	26.3 ± 18.8
p-value^a a Mann-Whitney head.	0.153	0.197	0.524	0.566	0.522	0.487	0.889	0.137

		PT^a a Spearman correlation.				IT^a a Spearman correlation.
		CD3	CD8	CD20	CD68	CD3	CD8	CD20	CD68
Lip
CD3	r	‒	0.019	0.400	^* * p< 0.05 versus other group (mean ± SD) 0.883	‒	0.982	0.000	−0.072
	p-value	‒	0.975	0.252	0.002	‒	0.018	1.000	0.843
CD8	r	‒	‒	0.880	−0.567	‒	‒	0.000	0.132
	p-value	‒	‒	0.120	0.433	‒	‒	1.000	0.868
CD20	r	‒	‒	‒	0.556	‒	‒	‒	0.000
	p-value	‒	‒	‒	0.076	‒	‒	‒	1.000
CD68	r	‒	‒	‒	‒	‒	‒	‒	‒
	p-value	‒	‒	‒	‒	‒	‒	‒	‒
ki67	r	‒	‒	‒	‒	‒	‒	‒	‒
	p-value	‒	‒	‒	‒	‒	‒	‒	‒
Queilitis
CD3	r	‒	^* * p< 0.05 versus other group (mean ± SD) 0.547	0.386	^* * p< 0.05 versus other group (mean ± SD) 0.637	-	−0.075	0.000	0.133
	p-value	‒	0.035	0.193	0.008	-	0.848	1.000	0.635
CD8	r	‒	-	0.396	^* * p< 0.05 versus other group (mean ± SD) 0.624	-	-	0.000	−0.072
	p-value	‒	-	0.203	0.017	-	-	1.000	0.865
CD20	r	‒	-	-	−0.185	-	-	-	0.000
	p-value	‒	-	-	0.526	-	-	-	1.000
CD68	r	‒	-	-	-	-	-	-	-
	p-value	‒	-	-	-	-	-	-	-
ki67	r	‒	-	-	-	-	-	-	-
	p-value	‒	-	-	-	-	-	-	-
LSCC
CD3	r	‒	^* * p< 0.05 versus other group (mean ± SD) 0.467	0.288	0.028	‒	0.266	0.220	0.121
	p-value	‒	0.004	0.084	0.872	‒	0.112	0.190	0.487
CD8	r	‒	‒	^* * p< 0.05 versus other group (mean ± SD) 0.390	0.185	‒	‒	^* * p< 0.05 versus other group (mean ± SD) 0.396	^* * p< 0.05 versus other group (mean ± SD) 0.411
	p-value	‒	‒	0.017	0.288	‒	‒	0.014	0.013
CD20	r	‒	‒	‒	−0.177	‒	‒	‒	0.204
	p-value	‒	‒	‒	0.301	‒	‒	‒	0.234
CD68	r	‒	‒	‒	‒	‒	‒	‒	‒
	p-value	‒	‒	‒	‒	‒	‒	‒	‒
ki67	r	‒	‒	‒	‒	‒	‒	‒	‒
	p-value	‒	‒	‒	‒	‒	‒	‒	‒

	IT vs. PT
	CD3^a a Spearman correlation.	CD8^a a Spearman correlation.	CD20^a a Spearman correlation.	CD68^a a Spearman correlation.
Lip
r	0.551	−0.498	0.000	0.086
p-value	0.099	0.502	1.000	0.791
Queilitis
r	^* * p< 0.05 versus other group (mean ± SD) 0.871	^* * p< 0.05 versus other group (mean ± SD) 0.641	0.000	0.320
p-value	<0.001	0.025	1.000	0.211
LSCC
r	^* * p< 0.05 versus other group (mean ± SD) 0.474	^* * p< 0.05 versus other group (mean ± SD) 0.521	0.265	^* * p< 0.05 versus other group (mean ± SD) 0.363
p-value	0.002	0.001	0.107	0.030

Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Sede da Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico Facial, Av. Indianópolia, 1287, 04063-002 São Paulo/SP Brasil, Tel.: (0xx11) 5053-7500, Fax: (0xx11) 5053-7512 - São Paulo - SP - Brazil
E-mail: revista@aborlccf.org.br

Acompanhe os números deste periódico no seu leitor de RSS

[1] ⁎ Corresponding author. E-mail: paulo_goberlanio@yahoo.com.br (P.G. Silva)