P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation
Abstract
:Simple Summary
Abstract
1. Introduction
2. Material and Methods
2.1. Case Selection
2.2. Histological Revision
2.3. HPV Testing, p16 IHC, and Criteria for Classifying a Tumour as HPV-Associated or HPV-Independent
2.4. p53 IHC Staining and Evaluation
2.5. Whole Exome Sequencing and Bioinformatic Analysis
2.6. Attribution of TP53 Mutational Status
2.7. Statistical Analysis
3. Results
3.1. Cases Included in the Study and Association with HPV
3.2. Characteristics of the Overall Series
3.3. TP53 Mutations
3.4. Agreement between p53 IHC and TP53 Mutational Status and Interobserver Agreement
3.5. p53 IHC Patterns and TP53 Status in HPV-Associated PSCC
3.6. p53 IHC Patterns and TP53 Status in HPV-Independent PSCC
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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HPV-Associated PSCC (n = 12) | HPV-Independent PSCC (n = 28) | p | |
---|---|---|---|
Mean age (years) ± standard deviation | 65.2 ± 14.9 | 69.1± 13.1 | 0.23 |
Histological subtype | <0.001 | ||
Usual/verrucous | 3 (25.0%) | 27 (96.4%) | |
Basaloid/warty/lymphoepithelioma-like | 9 (75.0%) | 1 (3.6%) | |
Vascular invasion | 1 (8.3%) | 3 (10.7%) | 0.8 |
Perineural invasion | 1 (8.3%) | 2 (7.1%) | 0.8 |
Lymph node metastases | 3 (25.0%) | 8 (28.6%) | 0.8 |
Stage | 1 | ||
Initial (I) | 6 (50.0%) | 14 (50.0%) | |
Advanced (II/III/IV) | 6 (50.0%) | 14 (50.0%) | |
Treatment | 1 | ||
Surgery | 10 (83.3%) | 21 (75.0%) | |
Surgery + radiation and/or chemotherapy | 2 (16.6%) | 7 (25.0%) |
p53 Immunohistochemistry Evaluation | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Pattern-Based * | Conventional ** | TP53 Status | |||||||||
Observer 1 | Observer 2 | Observer 3 | Consensus | Observer 4 | |||||||
Normal | Abnormal | Normal | Abnormal | Normal | Abnormal | Normal | Abnormal | Normal | Abnormal | ||
TP53 wild-type | 15 | 3 | 14 | 4 | 13 | 5 | 16 | 2 | 16 | 2 | 18 |
TP53 mutant | 2 | 20 | 6 | 16 | 2 | 20 | 1 | 21 | 10 | 12 | 22 |
Total | 17 | 23 | 20 | 20 | 15 | 25 | 17 | 23 | 26 | 14 | 40 |
Sensitivity | 90.9 (70.8–98.9) | 72.7 (49.8–89.3) | 90.9 (70.8–98.9) | 95.5 (77.2–99.9) | 54.5 (32.2–75.6) | ||||||
Specificity | 83.3 (58.6–96.4) | 77.8 (52.4–93.6) | 72.2 (46.5–90.3) | 88.9 (65.3–98.6) | 88.9 (65.3–98.6) | ||||||
Accuracy | 87.5 (73.2–95.8) | 75.0 (58.8–87.3) | 82.5 (67.2–92.7) | 92.5 (79.6–98.4) | 70.0 (53.5–83.4) |
Case | HPV Status | p53 IHC Status | p53 IHC Pattern | TP53 Status | TP53 Variant (Protein Change) | Type of TP53 Mutation | VAF | Clinical Significance of TP53 Variant | TP53 Copy Number Status |
---|---|---|---|---|---|---|---|---|---|
1 | Pos | Normal | Scatt | Wt | - | - | - | - | Normal |
2 | Pos | Normal | Scatt | Wt | - | - | - | - | Normal |
3 | Pos | Normal | Scatt | Wt | - | - | - | - | Normal |
4 | Pos | Normal | Scatt | Wt | - | - | - | - | Normal |
5 | Pos | Normal | Scatt | Wt | - | - | - | - | Normal |
6 | Pos | Normal | Scatt | Wt | - | - | - | - | Normal |
7 | Pos | Normal | Scatt | Wt | - | - | - | - | Gain |
8 | Pos | Normal | Scatt | Wt | - | - | - | - | Gain |
9 | Pos | Normal | Mid-ep | Wt | - | - | - | - | Normal |
10 | Pos | Normal | Mid-ep | Wt | - | - | - | - | Normal |
11 | Pos | Abnormal | Diff OE | Mut | c.637C>T (R213*) | Nonsense | 0.05 | Pathogenic | Loss |
12 | Pos | Abnormal | Diff OE | Wt | - | - | - | - | Normal |
13 | Neg | Normal | Scatt | Wt | - | - | - | - | Normal |
14 | Neg | Normal | Scatt | Wt | - | - | - | - | Normal |
15 | Neg | Normal | Scatt | Wt | - | - | - | - | Normal |
16 | Neg | Normal | Scatt | Wt | - | - | - | - | Normal |
17 | Neg | Normal | Scatt | Wt | - | - | - | - | Normal |
18 | Neg | Normal | Scatt | Mut | c.251C>T (A84V) | Missense | 0.04 | Likely benign | Normal |
19 | Neg | Normal | Scatt | Wt | - | - | - | - | Gain |
20 | Neg | Abnormal | Null | Mut | - | - | - | - | Loss |
21 | Neg | Abnormal | Null | Mut | - | - | - | - | Loss |
22 | Neg | Abnormal | Diff OE | Mut | - | - | - | - | Loss |
23 | Neg | Abnormal | Diff OE | Wt | - | - | - | - | Normal |
24 | Neg | Abnormal | Basal | Mut | c.530C>T (P177L) | Missense | 0.27 | Likely pathogenic/uncertain | Normal |
25 | Neg | Abnormal | Cyt | Mut | c.574G>A (A192T) | Missense | 0.04 | Uncertain | Normal |
26 | Neg | Abnormal | Diff OE | Mut | c.1082G>A (G361E) | Missense | 0.07 | Uncertain | Normal |
27 | Neg | Abnormal | Diff OE | Mut | c.919+1G>A (-) | Splice-site | 0.06 | Likely pathogenic | Normal |
28 | Neg | Abnormal | Diff OE | Mut | c.527G>T (C176F) | Missense | 0.12 | Pathogenic/likely pathogenic | Normal |
29 | Neg | Abnormal | Diff OE | Mut | c.843C>G (D281E) | Missense | 0.16 | Uncertain/likely pathogenic | Normal |
30 | Neg | Abnormal | Cyt | Mut | c.991C>T (Q331*) | Nonsense | 0.11 | Pathogenic | Normal |
31 | Neg | Abnormal | Diff OE | Mut | c.335G>A (S112N) | Missense | 0.79 | Uncertain | Normal |
32 | Neg | Abnormal | Diff OE | Mut | c.524G>A (R175H) | Missense | 0.12 | Likely Pathogenic/uncertain | Gain |
33 | Neg | Abnormal | Diff OE | Mut | c.799C>T (R267W) | Missense | 0.05 | Pathogenic/likely pathogenic | Gain |
34 | Neg | Abnormal | Diff OE | Mut | c.844C>T (R282W) | Missense | 0.26 | Pathogenic/likely pahogenic | Normal |
35 | Neg | Abnormal | Null | Mut | c.637C>T (R213*) | Nonsense | 0.32 | Pathogenic | Normal |
36 | Neg | Abnormal | Null | Mut | c.273dupT (-) | Frameshift | 0.65 | Not found | Normal |
37 | Neg | Abnormal | Null | Mut | c.817C>T (R273C) | Missense | 0.05 | Pathogenic/likely pathogenic | Normal |
38 | Neg | Abnormal | Null | Mut | c.461G>A (G154D); c.276+1G>C (-) | Missense; Splice-site | 0.05; 0.64 | Uncertain; Not found | Normal |
39 | Neg | Abnormal | Diff OE | Mut | c.517G>A (V173M); c.637C>T (R213*) | Missense; Nonsense | 0.21; 0.1 | Pathogenic; Pathogenic | Normal |
40 | Neg | Abnormal | Diff OE | Mut | c.524G>A (R175H) | Missense | 0.44 | Likely Pathogenic/uncertain | Normal |
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Trias, I.; Saco, A.; Marimon, L.; López del Campo, R.; Manzotti, C.; Ordi, O.; del Pino, M.; Pérez, F.M.; Vega, N.; Alós, S.; et al. P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation. Cancers 2023, 15, 2719. https://doi.org/10.3390/cancers15102719
Trias I, Saco A, Marimon L, López del Campo R, Manzotti C, Ordi O, del Pino M, Pérez FM, Vega N, Alós S, et al. P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation. Cancers. 2023; 15(10):2719. https://doi.org/10.3390/cancers15102719
Chicago/Turabian StyleTrias, Isabel, Adela Saco, Lorena Marimon, Ricardo López del Campo, Carolina Manzotti, Oriol Ordi, Marta del Pino, Francisco M. Pérez, Naiara Vega, Silvia Alós, and et al. 2023. "P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation" Cancers 15, no. 10: 2719. https://doi.org/10.3390/cancers15102719