Investigation of HEG1, VISTA (VSIR) and PD-L1 expression levels in malignant mesothelioma by immunohistochemical methods and their relationship with histological subtypes

Figures & data

Table 1. Distribution of mesothelial patients according to demographic, histopathological and immunohistochemical characteristics.

		n (%)
HISTOLOGIC SUBTYPE	Epithelioid	45 (65.2)
	Sarcomatoid	10 (14.5)
	Biphasic	9 (13.1)
	Well differentiated papillary mesothelial tumor	3 (4.3)
	Atypical mesothelial hyperplasia	2 (2.8)
AGE		62±10.94
SEX	F/M	30/39 (43/56)
LOCATION	Pleura	59 (85.5)
	Peritoneum	7 (10)
	Testis	3 (4.3)
HEG1	Negative	1 (%1.4)
	Positive	68 (98.6)
VISTA	Negative	6 (%8.7)
	Positive	63 (%91.3)
PD-L1	Negative	46 (%66.6)
	Positive	23 (33.3)

VISTA:V-domain Ig suppressor of T cell activation; PD-L1: programmed death ligand 1; HEG1: Sialylated protein HEG homolog 1.

Figure 1. HEG1 expression in malignant mesothelioma subtypes. (A) Strong HEG1 expression in high-grade epithelioid malignant mesothelioma (immunoperoxidase, 100X). (B) Biphasic mesothelioma; strong HEG1 expression (arrow) in epithelioid areas, weak HEG1 expression (star) in sarcomatoid areas (immunoperoxidase, 100X). Scale bar = 500 µm.

Table 2. HEG1 Expression status according to tumor types.

HEG1 immunoreactivity
Tumor Type	Negative	Score 3	Score 4	Score 5	Score 6
Pleura	1	2	8	12	36
Epithelioid	1	1	4	7	25
Low grade	1	1	1	1	17
High grade	0	0	3	6	8
Sarcomatoid	0	1	4	3	2
Biphasic	0	0	0	1	7
WDPMP	0	0	0	1	0
AMH	0	0	0	0	2
Peritoneum	0	1	0	2	4
Epitheloid	0	1	0	1	2
Biphasic	0	0	0	0	1
WDMP	0	0	0	1	1
Testis	0	0	0	0	3
Pulmonary adenocarcinoma	3	0	0	0	0
SCC	3	0	0	0	0
Sarcomatoid carcinoma	1	0	0	0	0
Other carcinomas	8	0	0	0	0
Malignant melanoma	1	0	0	0	0
SFT	1	0	0	0	0
Ewing sarcoma	1	0	0	0	0
MIFS	1	0	0	0	0

WDMP: Well differentiated papillary mesothelial tumor; AMH: atypical mesothelial hyperplasia; SCC Squamous cell carcinoma; SFT: Solitary fibrous tumor; MIFS: Myxoinflammatory fibroblastic sarcoma; HEG1: Sialylated protein HEG homolog 1.

Table 3. VISTA and PD-L1 ımmunoreactivity in mesothelial lesion subgroups.

HISTOLOGIC SUBTYPE	IMMUNOHISTOCHEMICAL EXPRESSİON	VISTA		PD-L1
		FREQUENCY	%	FREQUENCY	%
Epithelioid MM	Negative	1	2	32	71
	%1-49	15	33	11	25
	%50-100	29	65	2	4
Sarcomatoid MM	Negative	4	40	2	20
	%1-49	5	50	4	40
	%50-100	1	10	4	40
Biphasic MM	Negative	1	11	6	67
	%1-49	6	67	3	33
	%50-100	2	22	0	0
WDMT	Negative	0	0	3	100
	%1-49	1	33	0	0
	%50-100	2	67	0	0
AMH	Negative	0	0	2	100
	%1-49	0	0	0	0
	%50-100	2	100	0	0
p	0,00

MM: Malignant mesothelioma; WDPMP: Well differentiated papillary mesothelial tumor; AMH: atypical mesothelial hyperplasia; VISTA: V-domain Ig suppressor of T cell activation; PD-L1: programmed death ligand 1.

Figure 2. VISTA and PD-L1 expression levels in malignant mesothelioma subtypes. (A) Strong membranous VISTA expression in epithelioid mesothelioma (immunoperoxidase, 100X). (B) Biphasic mesothelioma: Strong VISTA expression (arrow) in epithelioid areas, VISTA negative (star) in sarcomatoid areas (immunoperoxidase; 100X) C. Strong membranous PD-L1 positivity in sarcomatoid mesothelioma (immunoperoxidase, 100X). (D) Focal, weak PD-L1 positivity (arrow) in biphasic mesothelioma (immunoperoxidase, 100X). Scale bar = 500 µm.

Table 4. The state of VISTA and PD-L1 expressions in epithelioid malignant mesotheliomas according to the histological degree.

HISTOLOGIC GRADE	IMMUNOHISTOCHEMICAL EXPRESSION	VISTA		PD-L1
		FREQUENCY	%	FREQUENCY	%
Low Grade	Negative	1	4.7	20	95.3
	Positive	20	95.3	1	4.7
High Grade	Negative	0	0	7	41.1
	Positive	17	100	10	58.9
p		0.63		0.000

VISTA: V-domain Ig suppressor of T cell activation; PD-L1: programmed death ligand 1.

Table 5. Comparison of VISTA and PD-L1 expressions in mesothelial lesions.

VISTA
PD-L1	Negative	Moderate	Strong	Total
Negative	2	16	22	41
Moderate	2	7	9	17
Strong	2	3	1	6
Total	6	26	32	64

VISTA: V-domain Ig suppressor of T cell activation; PD-L1: programmed death ligand 1.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [UA], upon reasonable request.