Immunohistochemical expression of Ki67, EGFR and TRKC and their
               correlation with prognostic factors in medulloblastoma

Sobral, Ana Cristina Lira; Moreschi Neto, Victor; Traiano, Gabriela; Rosales, Jeana; Harada, Luana E.; Percicote, Ana Paula; Gugelmin, Elizabeth Schneider; Noronha, Lúcia de

doi:10.5935/1676-2444.20140030

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Pathology • J. Bras. Patol. Med. Lab. 50 (4) • Jul-Aug 2014 • https://doi.org/10.5935/1676-2444.20140030 copy

Immunohistochemical expression of Ki67, EGFR and TRKC and their correlation with prognostic factors in medulloblastoma

A expressão imuno-histoquímica de Ki67, EGFR E TRKC e sua correlação com fatores prognósticos em meduloblastomas

Authorship SCIMAGO INSTITUTIONS RANKINGS

Introduction:

Medulloblastoma is a malignant embryonal tumor of the cerebellum with poor prognosis. The treatment is based only on clinical criteria, such as risk group that only considers age, extent of tumor resection, recurrence, and metastasis.

Objective:

To evaluate a possible relationship between the immunoexpression of biomarkers (Ki67, receptor neutrophin-3 [TRKC], epidermal growth factor receptor [EGFR], B-cell lymphoma 2 [Bcl-2], and cyclin-D1), and the classical clinical prognostic factors of medulloblastoma.

Material and method:

thirty-five samples of pediatric medulloblastoma free of neoadjuvant chemotherapy were separated and reviewed for their histopathological classification; two areas representative of tumor were used in the construction of tissue microarrays. The following clinical data from 29 patients were used for comparison with the biomarkers expression: patient's age, presence or absence of complete tumor resection, staging patient's risk group, presence or absence of metastases, presence or absence of postoperative chemotherapy, and presence or absence of recurrence. Clinical follow-up of the study ranged from two to thirteen years, and cases with fatal outcome were also analyzed.

Results:

Patients with upper age showed higher expression of TRKC (p = 0.033). There was inversely proportional and statistically significant correlation between TRKC and Ki67 (p = 0.027). There was no statistical significance in the analysis of EGFR, Bcl2, and cyclin-D1.

Conclusion:

The immunoexpression of TRKC might be considered a biomarker related to tumors with better prognosis in patients with medulloblastoma, contributing to better risk groups' stratification.

medulloblastoma; TRKC; Ki67; EGFR; prognosis; biological behavior

Clinicopathologic variables		Frequency	Percentage
Age at prognosis (n = 29)
	< 3	10	34.5
	≥ 3	19	65.5
Presence of complete resection (n = 29)
	Yes	14	48.3
	No	15	51.7
Presence of postoperative recurrence (n = 29)
	Yes	9	31
	No	20	69
Presence of metastases at diagnosis (n = 29)
	Yes	0	0
	No	29	100
Postoperative chemotherapy (n = 29)
	Yes	26	89.7
	No	3	10.3
Death (n= 29)
	Yes	3	10.3
	No	26	89.7
Risk group (n = 29)
	Low	9	31
	High	20	69
	Variables	Average (SD)	Median
TRKC immunostaining (n = 35)		0.0056 (0.0016)	0.0056
EGRF immunostaining (n = 35)		0.0012 (0.0007)	0.0011
Ki67 immunostaining (n = 35)		29.9 (29.5)	26.2
Age at diagnosis (n= 29)		4.8 (3.3)	4.0
Time of postsurgical recurrence (n = 9)		1.7 (0.4)	2.0
Time until death (n= 3)		32.7 (24.4)	25.0

Marker	Clinicopathologic variables	Average (SD)	Median	p values
Total surgical resection (n = 29)
TRKC	No	0.0054 (0.0012)	0.0052
	Yes	0.0056 (0.0012)	0.0059	0.905
EGFR	No	0.0013 (0.0007)	0.0011
	Yes	0.0012 (0.0008)	0.0009	0.458
Ki67	No	32.1 (32.7)	43.5
	Yes	27.1 (25.6)	29.9	0.650
Postsurgical recurrence (n = 29)
TRKC	No	0.0055 (0.0012)	0.0052
	Yes	0.0056 (0.0014)	0.0059	0.735
EGFR	No	0.0011 (0.0007)	0.0009
	Yes	0.0015 (0.0009)	0.0014	0.360
Ki67	No	31.5 (31.0)	33.5
	Yes	24.8 (23.7)	28.0	0.775
Death
TRKC	No	0.0055 (0.0013)	0.0059
	Yes	0.0052 (0.0011)	0.0052	0.689
EGFR	No	0.0012 (0.0007)	0.001
	Yes	0.0016 (0.0013)	0.0009	0.743
Ki67	No	27.9 (28.1)	29.9
	Yes	42.3 (36.8)	60.0	0.483
Age at diagnosis (n = 29)
TRKC	< 3	0.0051	0.0047
	≥ 3	0.0057	0.0061	0.232
EGFR	< 3	0.0012	0.001
	≥ 3	0.0013	0.001	0.820
Ki67	< 3	38.6	39
	≥ 3	24.9	19.5	0.348
Risk group (n = 29)
TRKC	High	0.0054	0.00495
	Low	0.00572	0.00609	0.607
EGFR	High	0.00128	0.00104
	Low	0.00118	0.0008	0.381
Ki67	High	30.51	36.25
	Low	27.48	26.2	0.831

Variables	Spearman correlation coefficient	p value
Age at diagnosis and TRKC	0.41	0.033
Age at diagnosis and EGFR	0.07	0.737
Age at diagnosis and Ki67	-0.33	0.088
TRKC and EGFR	0.32	0.071
TRKC and Ki67	-0.38	0.027
EGFR and Ki67	-0.01	0.957

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[1] MAILING ADDRESS: Lúcia de Noronha, Laboratório de Patologia Experimental; Escola de Medicina da Pontifícia Universidade Católica do Paraná; Rua Imaculada Conceição, 1.155; Prado Velho; CEP: 80215-901; Curitiba-PR, Brazil; Phone: +55 (41) 3271-2264; Fax: +55 (41) 3271-1621; e-mail: lnno@terra.com.br.