Molecular correlates of invasion pattern in HPV-associated endocervical adenocarcinoma : emergence of two distinct risk-stratified tiers
© 2023 John Wiley & Sons Ltd..
BACKGROUND: The pattern-based (Silva) classification of invasive human papilloma virus (HPV)-associated endocervical adenocarcinomas (HPVA) is an established and reproducible method to predict outcomes for this otherwise stage-dependent group of tumours. Previous studies utilising targeted sequencing have shown a correlation between mutational profiles and an invasive pattern. However, such correlation has not been explored using comprehensive molecular testing.
DESIGN: Clinicopathologic data including invasive pattern (Silva groups A, B, and C) was collected for a cohort of invasive HPVA, which previously underwent massive parallel sequencing using a panel covering 447 genes. Pathogenic alterations, molecular signatures, tumour mutational burden (TMB), and copy number alterations (CNA) were correlated with pattern of invasion.
RESULTS: Forty five HPVA (11 pattern A, 17 pattern B, and 17 pattern C tumours) were included. Patients with pattern A presented at stage I with no involved lymph nodes or evidence of recurrence (in those with >2 months of follow-up). Patterns B and C patients also mostly presented at stage I with negative lymph nodes, but had a greater frequency of recurrence; 3/17 pattern B and 1/17 pattern C HPVAs harboured lymphovascular space invasion (LVI). An APOBEC mutational signature was detected only in Silva pattern C tumours (5/17), and pathogenic PIK3CA changes were detected only in destructively invasive HPVA (patterns B and C). When cases were grouped as low-risk (pattern A and pattern B without LVI) and high-risk (pattern B with LVI and pattern C), high-risk tumours were enriched in mutations in PIK3CA, ATRX, and ERBB2. There was a statistically significant difference in TMB between low-risk and high-risk pattern tumours (P = 0.006), as well as between Pattern C tumours with and without an APOBEC signature (P = 0.002). CNA burden increased from pattern A to C.
CONCLUSION: Our findings further indicate that key molecular events in HPVA correlate with the morphologic invasive properties of the tumour and their aggressiveness. Pattern B tumours with LVI clustered with pattern C tumours, whereas pattern B tumours without LVI approached pattern A genotypically. Our study provides a biologic foundation for consolidating the Silva system into low-risk (pattern A + B without LVI) and high-risk (pattern B with LVI and pattern C) categories.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:82 |
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| Enthalten in: |
Histopathology - 82(2023), 7 vom: 27. Juni, Seite 1067-1078 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sharma, Aarti E [VerfasserIn] |
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| Links: |
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| Themen: |
APOBEC |
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| Anmerkungen: |
Date Completed 17.05.2023 Date Revised 14.06.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/his.14893 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM353557900 |
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| 100 | 1 | |a Sharma, Aarti E |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Molecular correlates of invasion pattern in HPV-associated endocervical adenocarcinoma |b emergence of two distinct risk-stratified tiers |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 14.06.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: The pattern-based (Silva) classification of invasive human papilloma virus (HPV)-associated endocervical adenocarcinomas (HPVA) is an established and reproducible method to predict outcomes for this otherwise stage-dependent group of tumours. Previous studies utilising targeted sequencing have shown a correlation between mutational profiles and an invasive pattern. However, such correlation has not been explored using comprehensive molecular testing | ||
| 520 | |a DESIGN: Clinicopathologic data including invasive pattern (Silva groups A, B, and C) was collected for a cohort of invasive HPVA, which previously underwent massive parallel sequencing using a panel covering 447 genes. Pathogenic alterations, molecular signatures, tumour mutational burden (TMB), and copy number alterations (CNA) were correlated with pattern of invasion | ||
| 520 | |a RESULTS: Forty five HPVA (11 pattern A, 17 pattern B, and 17 pattern C tumours) were included. Patients with pattern A presented at stage I with no involved lymph nodes or evidence of recurrence (in those with >2 months of follow-up). Patterns B and C patients also mostly presented at stage I with negative lymph nodes, but had a greater frequency of recurrence; 3/17 pattern B and 1/17 pattern C HPVAs harboured lymphovascular space invasion (LVI). An APOBEC mutational signature was detected only in Silva pattern C tumours (5/17), and pathogenic PIK3CA changes were detected only in destructively invasive HPVA (patterns B and C). When cases were grouped as low-risk (pattern A and pattern B without LVI) and high-risk (pattern B with LVI and pattern C), high-risk tumours were enriched in mutations in PIK3CA, ATRX, and ERBB2. There was a statistically significant difference in TMB between low-risk and high-risk pattern tumours (P = 0.006), as well as between Pattern C tumours with and without an APOBEC signature (P = 0.002). CNA burden increased from pattern A to C | ||
| 520 | |a CONCLUSION: Our findings further indicate that key molecular events in HPVA correlate with the morphologic invasive properties of the tumour and their aggressiveness. Pattern B tumours with LVI clustered with pattern C tumours, whereas pattern B tumours without LVI approached pattern A genotypically. Our study provides a biologic foundation for consolidating the Silva system into low-risk (pattern A + B without LVI) and high-risk (pattern B with LVI and pattern C) categories | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a PIK3CA | |
| 650 | 4 | |a APOBEC | |
| 650 | 4 | |a HPV | |
| 650 | 4 | |a Next generation sequencing | |
| 650 | 4 | |a Silva classification | |
| 650 | 4 | |a invasive endocervical adenocarcinoma | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 700 | 1 | |a Hodgson, Anjelica J |e verfasserin |4 aut | |
| 700 | 1 | |a Howitt, Brooke E |e verfasserin |4 aut | |
| 700 | 1 | |a Olkhov-Mitsel, Ekaterina |e verfasserin |4 aut | |
| 700 | 1 | |a Djordevic, Bojana |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Kay J |e verfasserin |4 aut | |
| 700 | 1 | |a Nucci, Marisa R |e verfasserin |4 aut | |
| 700 | 1 | |a Parra-Herran, Carlos |e verfasserin |4 aut | |
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