J Hematol

Journal of Hematology, ISSN 1927-1212 print, 1927-1220 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Hematol and Elmer Press Inc

Journal website https://www.thejh.org

Short Communication

Volume 13, Number 5, October 2024, pages 200-206

Utility of p53 Immunohistochemical Staining for Risk Stratification of Mantle Cell Lymphoma

Figure 1. A representative case of mantle cell lymphoma. (a) Lymph node effaced by a neoplastic lymphoid process (H&E, × 7). (b) High-power image of a monotonous population of small to medium sized lymphocytes with irregular nuclear borders (H&E, × 400). (c) Cyclin D1 positivity confirming the diagnosis of mantle cell lymphoma (c: × 7, d: × 400). H&E: hematoxylin and eosin.

Figure 2. Immunohistochemical staining patterns in two TP53-pos cases (a-b and c-e) and a representative TP53-neg case (f-h). (a-b) Positive p53 IHC staining in TP53-pos MCL at low (a, × 10) and high (b, × 200) magnification. (c-e) Null p53 IHC in a TP53-pos MCL case (c, × 200), with rare non-neoplastic cells serving as internal control; this case was negative for SOX11 IHC (d, × 200) and had a high Ki-67 index (e, × 200). (f-h) Negative p53 IHC in TP53-neg MCL at low (f, × 10) and high (g, × 200) magnification; this tumor was positive for SOX11 IHC (h, × 200). IHC: immunohistochemistry; MCL: mantle cell lymphoma.

**Table 1.** Clinical and Disease Characteristics Stratified by *TP53* Mutational Status (A), Including Variant and IHC Details of 13 *TP53*-Mutant Cases (B)
A	TP53 positive (n = 13)	TP53 negative (n = 34)	P
Mean age (years)	67	67	0.87
Sex (n, %)			0.66
Male	10 (77)	24 (71)
Female	3 (23)	10 (29)
Location (n, %)			0.14
Nodal/mixed	13 (100)	29 (85)
Extranodal	0 (0)	5 (15)
Ki-67 index (n, %)			0.39
No. ≥ 30%	12 (92)	28 (82)
No. < 30%	1 (8)	6 (18)
SOX11 IHC^a (n, %)			0.045
Positive	10 (77)	28/29 (97)
Negative	3(23)	1/29 (3)
p53 IHC (n, %)			< 0.00001
Positive (aberrant)	11 (85)	0 (0)
Negative (wild type)	2 (15)	34 (100)
^aSOX11 was available for only 29/34 of TP53 negative cases. ^bFor tumors with > 1 variant, the highest level of impact/pathogenicity is listed. IHC: immunohistochemistry; N: negative; P: positive; VAF: variant allele frequency.
TP53 c.559 +1G>T, splice site	0.36	Pathogenic	N	P
TP53 c.850A>C, p.T284P	0.23	Likely pathogenic	N	P
TP53 c.584T>C, p.I195T	0.36	Likely pathogenic	P	P
TP53 c.711G>A, p.M237I TP53 c.131_132dup, p.L45fs TP53 c.493_516dup, p.Q165_172dup	0.14 0.36 0.32	Pathogenic	P	P
TP53 c.997delC, p.R333fs	0.84	Pathogenic	P	P
TP53 c.376T>G; p.Y126D	0.22	Likely pathogenic	P	N
TP53 c.376T>G; p.Y126D TP53 c.721T>C; p.S241P TP53 c.97-1G>A; splice site	0.22 0.43 0.42	Pathogenic	P	N
TP53 c.524G>A; p.R175H	0.71	Pathogenic	P	P
TP53 c.743 G>T p.R248L	0.48	Pathogenic	P	P
TP53 c.524G>A, p.R175H	0.61	Pathogenic	P	P
TP53 c.281C>G; p.S94	0.95	Pathogenic	P (null)	N
TP53 c.785G>T; p.G262V	0.85	Likely pathogenic	P	P
TP53 c.733G>A; p.G245S TP53 c.630C>A; p.N210K TP53 c.470T>A; p.V157D	0.50 0.10 0.06	Pathogenic	P	P

Table 1. Clinical and Disease Characteristics Stratified by TP53 Mutational Status (A), Including Variant and IHC Details of 13 TP53-Mutant Cases (B)

TP53 positive (n = 13)

TP53 negative (n = 34)

Mean age (years)

0.87

Sex (n, %)

0.66

Male

10 (77)

24 (71)

Female

3 (23)

10 (29)

Location (n, %)

0.14

Nodal/mixed

13 (100)

29 (85)

Extranodal

0 (0)

5 (15)

Ki-67 index (n, %)

0.39

No. ≥ 30%

12 (92)

28 (82)

No. < 30%

1 (8)

6 (18)

SOX11 IHC^a (n, %)

0.045

Positive

10 (77)

28/29 (97)

Negative

3(23)

1/29 (3)

p53 IHC (n, %)

< 0.00001

Positive (aberrant)

11 (85)

0 (0)

Negative (wild type)

2 (15)

34 (100)

B. Variant

VAF

Clinical significance^b

P53 IHC

SOX11

^aSOX11 was available for only 29/34 of TP53 negative cases. ^bFor tumors with > 1 variant, the highest level of impact/pathogenicity is listed. IHC: immunohistochemistry; N: negative; P: positive; VAF: variant allele frequency.

TP53 c.559 +1G>T, splice site

0.36

Pathogenic

TP53 c.850A>C, p.T284P

0.23

Likely pathogenic

TP53 c.584T>C, p.I195T

0.36

Likely pathogenic

TP53 c.711G>A, p.M237I
TP53 c.131_132dup, p.L45fs
TP53 c.493_516dup, p.Q165_172dup

0.14
0.36
0.32

Pathogenic

TP53 c.997delC, p.R333fs

0.84

Pathogenic

TP53 c.376T>G; p.Y126D

0.22

Likely pathogenic

TP53 c.376T>G; p.Y126D
TP53 c.721T>C; p.S241P
TP53 c.97-1G>A; splice site

0.22
0.43
0.42

Pathogenic

TP53 c.524G>A; p.R175H

0.71

Pathogenic

TP53 c.743 G>T p.R248L

0.48

Pathogenic

TP53 c.524G>A, p.R175H

0.61

Pathogenic

TP53 c.281C>G; p.S94

0.95

Pathogenic

P (null)

TP53 c.785G>T; p.G262V

0.85

Likely pathogenic

TP53 c.733G>A; p.G245S
TP53 c.630C>A; p.N210K
TP53 c.470T>A; p.V157D

0.50
0.10
0.06

Pathogenic