The prognostic importance of PD-L1, PTEN, PHH3, and KI-67 expressions in invasive breast carcinoma

Imamoglu, Eda Hilal; Duzcu, Selma Erdogan

doi:10.1590/1806-9282.20220317

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Revista da Associação Médica Brasileira

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Original Article • Rev. Assoc. Med. Bras. 68 (12) • 2022 • https://doi.org/10.1590/1806-9282.20220317 copy

The prognostic importance of PD-L1, PTEN, PHH3, and KI-67 expressions in invasive breast carcinoma

Authorship SCIMAGO INSTITUTIONS RANKINGS

SUMMARY

OBJECTIVE:

The aim of this study was to investigate the relationship of PD-L1, PTEN, PHH3, and Ki-67 immunohistochemical stain expressions with prognostic clinicopathological parameters in breast cancer.

METHODS:

Lumpectomy and mastectomy materials from 85 patients operated at the Department of Pathology, Bolu Abant Izzet Baysal University, Faculty of Medicine between 2014 and 2019 were retrospectively reviewed. PD-L1, PTEN, PHH3, and Ki-67 expressions were examined. Immunohistochemical staining results were compared with clinicopathological parameters and found to be associated with prognosis.

RESULTS:

A statistically significant correlation was found between PD-L1 and large tumor size, high histological grade, multifocality, and lymphovascular invasion. A statistically significant correlation was found between the loss of PTEN and large tumor size and histological grade. There was a statistically significant correlation between PHH3 and advanced age, large tumor size, and high histological grade. A statistically significant correlation was found between Ki-67 and large tumor size, high histological grade, and lymphovascular invasion.

CONCLUSION:

PD-L1, PTEN, PHH3, and Ki-67 are regarded as potential biomarkers that can be used to predict the prognosis of breast cancer and to develop targeted therapies.

Keywords
Carcinoma, ductal; Breast; Immunohistochemistry; Immune checkpoint inhibitors; Ki-67 antigen

Prognostic factors		PD-L1					PTEN
		Negative		Positive		p	<90		≥90		p-value
		n	%	N	%	p	n	%	n	%	p-value
Age	<40	5	7.8%	2	9.5%	0.67	4	9.5%	3	7.0%	0.60
Age	≥40	59	92.2%	19	90.5%	0.67	38	90.5%	40	93.0%	0.60
Gender	Female	62	96.9%	20	95.2%	0.73	42	100.0%	40	93.0%	0.08
Gender	Male	2	3.1%	1	4.8%	0.73	0	0.0%	3	7.0%	0.08
Tumor Localization	Right	31	48.4%	13	61.9%	0.01*	25	59.5%	19	44.2%	0.11
Tumor Localization	Left	33	51.6%	8	38.1%	0.01*	17	40.5%	24	55.8%	0.11
Tumor size (cm)	<2	27	42.2%	7	33.3%	0.04*	14	33.3%	20	46.5%	0.03*
Tumor size (cm)	≥2	37	57.8%	14	66.7%	0.04*	28	66.7%	23	53.5%	0.03*
Histological grade	1	10	15.6%	1	4.8%	0.03*	7	16.7%	4	9.3%	0.03*
	2	37	57.8%	11	52.4%		25	59.5%	23	53.5%
	3	17	26.6%	9	42.9%		10	23.8%	16	37.2%
Lymphovascular invasion	None	38	59.4%	9	42.9%	0.01*	22	52.38%	25	58.1%	0.13
Lymphovascular invasion	Yes	26	40.6%	12	57.1%	0.01*	20	47.62%	18	41.9%	0.13
Perineural invasion	None	50	78.1%	16	76.2%	0.56	32	76.19%	34	79.07%	0.21
Perineural invasion	Yes	14	21.9%	5	23.8%	0.56	10	23.81%	9	20.93%	0.21
Pathologic T	T1	29	45.3%	7	33.3%	0.06	15	35.71%	21	48.84%	0.24
	T2	27	42.2%	13	61.9%		23	54.76%	17	39.53%
	T3	3	4.7%	1	4.8%		2	4.76%	2	4.65%
	T4	5	7.8%	0	0.0%		2	4.76%	3	6.98%
Pathologic N	N0	3	9.4%	0	0.0%	0.12	1	4.55%	2	9.09%	0.13
	N1	5	15.6%	2	16.7%		1	4.55%	6	27.27%
	N2	15	46.9%	8	66.7%		13	59.09%	10	45.45%
	N3	9	28.1%	2	16.7%		7	31.82%	4	18.18%
Pathologic M	M0	57	89.1%	21	100.0%	0.03*	38	90.48%	40	93.02%	0.11
Pathologic M	M1	7	10.9%	0	0.0%	0.03*	4	9.52%	3	6.98%	0.11
Stage	1A	20	31.3%	5	23.8%	0.14	12	28.57%	13	30.23%	0.25
	1B	1	1.6%	0	0.0%		0	0.00%	1	2.33%
	2A	12	18.8%	5	23.8%		9	21.43%	8	18.60%
	2B	9	14.1%	1	4.8%		4	9.52%	6	13.95%
	3A	7	10.9%	7	33.3%		7	16.67%	7	16.28%
	3B	2	3.1%	0	0.0%		0	0.00%	2	4.65%
	3C	10	15.6%	3	14.3%		9	21.43%	4	9.30%
	4	3	4.7%	0	0.0%		1	2.38%	2	4.65%
ER	Negative	7	10.9%	5	23.8%	0.03*	9	15.00%	3	12.00%	0.08
ER	Positive	57	89.1%	16	76.2%	0.03*	51	85.00%	22	88.00%	0.08
PR	Negative	11	17.2%	9	42.9%	0.01*	14	23.30%	6	24.00%	0.21
PR	Positive	53	82.8%	12	57.1%	0.01*	46	76.70%	19	76.00%	0.21
HER2	0	32	50.0%	8	38.1%	0.16	17	40.48%	23	53.49%	0.13
	1	12	18.8%	5	23.8%		10	23.81%	7	16.28%
	2	10	15.6%	4	19.0%		9	21.43%	5	11.63%
	3	10	15.6%	4	19.0%		6	14.29%	8	18.60%

Prognostic factors		PHH3					Ki-67
		<2		≥2		p	<20%		≥20%		p
		n	%	n	%	p	n	%	n	%	p
Tumor size (cm)	<2	23	46.9%	11	30.6%	0.01*	28	49.1%	6	21.4%	0.01*
Tumor size (cm)	≥2	26	53.1%	25	69.4%	0.01*	29	50.9%	22	78.6%	0.01*
Histological grade	1	10	20.4%	1	2.8%	0.02*	1	1.8%	0	0.0%	0.01*
	2	26	53.1%	22	61.1%		11	19.3%	0	0.0%
	3	13	26.5%	13	36.1%		35	61.4%	13	46.4%
Lymphovascular invasion	None	29	59.2%	18	50.0%	0.58	37	64.9%	10	35.7%	0.01*
Lymphovascular invasion	Yes	20	40.8%	18	50.0%	0.58	20	35.1%	18	64.3%	0.01*
Perineural invasion	None	39	79.6%	27	75.0%	0.01*	43	75.4%	23	82.1%	0.01*
Perineural invasion	Yes	10	20.4%	9	25.0%	0.01*	14	24.6%	5	17.9%	0.01*
Pathologic T	T1	24	49.0%	12	33.3%	0.05	29	50.9%	7	25.0%	0.05
	T2	20	40.8%	20	55.6%		23	40.4%	17	60.7%
	T3	2	4.1%	2	5.6%		3	5.3%	1	3.6%
	T4	3	6.1%	2	5.6%		2	3.5%	3	10.7%
Pathologic N	N0	2	8.0%	1	5.3%	0.36	1	3.7%	2	11.8%	0.28
	N1	3	12.0%	4	21.1%		4	14.8%	3	17.6%
	N2	15	60.0%	8	42.1%		14	51.9%	9	52.9%
	N3	5	20.0%	6	31.6%		8	29.6%	3	17.6%
Pathologic M	M0	45	91.8%	33	91.7%	0.51	53	93.0%	25	89.3%	0.30
Pathologic M	M1	4	8.2%	3	8.3%	0.51	4	7.0%	3	10.7%	0.30
Stage	1A	16	32.7%	9	25.0%	0.35	21	36.8%	4	14.3%	0.38
	1B	1	2.0%	0	0.0%		1	1.8%	0	0.0%
	2A	9	18.4%	8	22.2%		10	17.5%	7	25.0%
	2B	6	12.2%	4	11.1%		6	10.5%	4	14.3%
	3A	6	12.2%	8	22.2%		7	12.3%	7	25.0%
	3B	2	4.1%	0	0.0%		1	1.8%	1	3.6%
	3C	7	14.3%	6	16.7%		9	15.8%	4	14.3%
	4	2	4.1%	1	2.8%		2	3.5%	1	3.6%
ER	Negative	4	8.2%	8	22.2%	0.02*	4	7.0%	8	28.6%	0.01*
ER	Positive	45	91.8%	28	77.8%	0.02*	53	93.0%	20	71.4%	0.01*
PR	Negative	9	18.4%	11	30.6%	0.01*	8	14.0%	12	42.9%	0.01*
PR	Positive	40	81.6%	25	69.4%	0.01*	49	86.0%	16	57.1%	0.01*
HER2	0	9	18.4%	8	22.2%	0.05	31	54.4%	9	32.1%	0.07
	1	7	14.3%	7	19.4%		12	21.1%	5	17.9%
	2	8	16.3%	6	16.7%		10	17.5%	4	14.3%
	3	9	18.4%	8	22.2%		4	7.0%	10	35.7%

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[1] *Corresponding author: serdoganduzcu@hotmail.com