Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions

Verona E Bergshoeff; Maschenka C A Balkenhol; Annick Haesevoets; Andrea Ruland; Michelene N Chenault; Rik C Nelissen; Carine J Peutz; Ruud Clarijs; Jeroen A W M Van der Laak; Robert P Takes; Michiel W Van den Brekel; Marie-Louise F Van Velthuysen; Frans C S Ramaekers; Bernd Kremer; Ernst-Jan M Speel

doi:10.3390/cancers14133260

Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions

Verona E Bergshoeff^*, Maschenka C A Balkenhol, Annick Haesevoets, Andrea Ruland, Michelene N Chenault, Rik C Nelissen, Carine J Peutz, Ruud Clarijs, Jeroen A W M Van der Laak, Robert P Takes, Michiel W Van den Brekel, Marie-Louise F Van Velthuysen, Frans C S Ramaekers, Bernd Kremer, Ernst-Jan M Speel

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI.

METHODS: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (≥0.84 ≤ 1.16) was based on the mean CR +/- 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring > 2 chromosomes of chromosome 1 and/or 7 (PAN), was established (cut-off value for abnormal PAN ≥ 10%).

RESULTS: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%).

CONCLUSIONS: evaluation criteria for FISH 1c/7c based on PAN ≥ 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c/7c detection can be applied in combination with histopathological assessment.

Original language	English
Article number	3260
Number of pages	15
Journal	Cancers
Volume	14
Issue number	13
DOIs	https://doi.org/10.3390/cancers14133260
Publication status	Published - 3 Jul 2022

Keywords

CANCER
CELL CARCINOMAS
EPIDEMIOLOGY
EXPRESSION
FISH
HEAD
IN-SITU HYBRIDIZATION
LUNG
RESECTION MARGINS
RISK
TUMORS
chromosome instability
dysplasia
head and neck cancer
larynx
premalignant

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Bergshoeff, V. E., Balkenhol, M. C. A., Haesevoets, A., Ruland, A., Chenault, M. N., Nelissen, R. C., Peutz, C. J., Clarijs, R., Van der Laak, J. A. W. M., Takes, R. P., Van den Brekel, M. W., Van Velthuysen, M.-L. F., Ramaekers, F. C. S., Kremer, B., & Speel, E.-J. M. (2022). Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions. Cancers, 14(13), Article 3260. https://doi.org/10.3390/cancers14133260

@article{4b7ea431de814f69b19611e252187297,

title = "Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions",

abstract = "BACKGROUND: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI.METHODS: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (≥0.84 ≤ 1.16) was based on the mean CR +/- 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring > 2 chromosomes of chromosome 1 and/or 7 (PAN), was established (cut-off value for abnormal PAN ≥ 10%).RESULTS: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%).CONCLUSIONS: evaluation criteria for FISH 1c/7c based on PAN ≥ 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c/7c detection can be applied in combination with histopathological assessment.",

keywords = "CANCER, CELL CARCINOMAS, EPIDEMIOLOGY, EXPRESSION, FISH, HEAD, IN-SITU HYBRIDIZATION, LUNG, RESECTION MARGINS, RISK, TUMORS, chromosome instability, dysplasia, head and neck cancer, larynx, premalignant",

author = "Bergshoeff, {Verona E} and Balkenhol, {Maschenka C A} and Annick Haesevoets and Andrea Ruland and Chenault, {Michelene N} and Nelissen, {Rik C} and Peutz, {Carine J} and Ruud Clarijs and {Van der Laak}, {Jeroen A W M} and Takes, {Robert P} and {Van den Brekel}, {Michiel W} and {Van Velthuysen}, {Marie-Louise F} and Ramaekers, {Frans C S} and Bernd Kremer and Speel, {Ernst-Jan M}",

note = "Funding Information: This research was funded by Dutch Cancer Society (KWF, grant 2007-3935) and Health Foundation Limburg, the Netherlands (HFL). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

month = jul,

day = "3",

doi = "10.3390/cancers14133260",

language = "English",

volume = "14",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "13",

}

Bergshoeff, VE, Balkenhol, MCA, Haesevoets, A, Ruland, A, Chenault, MN, Nelissen, RC, Peutz, CJ, Clarijs, R, Van der Laak, JAWM, Takes, RP, Van den Brekel, MW, Van Velthuysen, M-LF, Ramaekers, FCS, Kremer, B & Speel, E-JM 2022, 'Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions', Cancers, vol. 14, no. 13, 3260. https://doi.org/10.3390/cancers14133260

TY - JOUR

T1 - Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions

AU - Bergshoeff, Verona E

AU - Balkenhol, Maschenka C A

AU - Haesevoets, Annick

AU - Ruland, Andrea

AU - Chenault, Michelene N

AU - Nelissen, Rik C

AU - Peutz, Carine J

AU - Clarijs, Ruud

AU - Van der Laak, Jeroen A W M

AU - Takes, Robert P

AU - Van den Brekel, Michiel W

AU - Van Velthuysen, Marie-Louise F

AU - Ramaekers, Frans C S

AU - Kremer, Bernd

AU - Speel, Ernst-Jan M

N1 - Funding Information: This research was funded by Dutch Cancer Society (KWF, grant 2007-3935) and Health Foundation Limburg, the Netherlands (HFL). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022/7/3

Y1 - 2022/7/3

N2 - BACKGROUND: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI.METHODS: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (≥0.84 ≤ 1.16) was based on the mean CR +/- 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring > 2 chromosomes of chromosome 1 and/or 7 (PAN), was established (cut-off value for abnormal PAN ≥ 10%).RESULTS: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%).CONCLUSIONS: evaluation criteria for FISH 1c/7c based on PAN ≥ 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c/7c detection can be applied in combination with histopathological assessment.

AB - BACKGROUND: The definition of objective, clinically applicable evaluation criteria for FISH 1c/7c in laryngeal precursor lesions for the detection of chromosome instability (CI). Copy Number Variations (CNV) for chromosomes 1 and 7 reflect the general ploidy status of premalignant head and neck lesions and can therefore be used as a marker for CI.METHODS: We performed dual-target FISH for chromosomes 1 and 7 centromeres on 4 µm formalin-fixed, paraffin-embedded tissue sections of 87 laryngeal premalignancies to detect CNVs. Thirty-five normal head and neck squamous cell samples were used as a control. First, the chromosome 7:1 ratio (CR) was evaluated per lesion. The normal range of CRs (≥0.84 ≤ 1.16) was based on the mean CR +/- 3 x SD found in the normal population. Second, the percentage of aberrant nuclei, harboring > 2 chromosomes of chromosome 1 and/or 7 (PAN), was established (cut-off value for abnormal PAN ≥ 10%).RESULTS: PAN showed a stronger correlation with malignant progression than CR (resp. OR 5.6, p = 0.001 and OR 3.8, p = 0.009). PAN combined with histopathology resulted in a prognostic model with an area under the ROC curve (AUC) of 0.75 (s.e. 0.061, sensitivity 71%, specificity 70%).CONCLUSIONS: evaluation criteria for FISH 1c/7c based on PAN ≥ 10% provide the best prognostic information on the risk of malignant progression of premalignant laryngeal lesions as compared with criteria based on the CR. FISH 1c/7c detection can be applied in combination with histopathological assessment.

KW - CANCER

KW - CELL CARCINOMAS

KW - EPIDEMIOLOGY

KW - EXPRESSION

KW - FISH

KW - HEAD

KW - IN-SITU HYBRIDIZATION

KW - LUNG

KW - RESECTION MARGINS

KW - RISK

KW - TUMORS

KW - chromosome instability

KW - dysplasia

KW - head and neck cancer

KW - larynx

KW - premalignant

U2 - 10.3390/cancers14133260

DO - 10.3390/cancers14133260

M3 - Article

C2 - 35805032

SN - 2072-6694

VL - 14

JO - Cancers

JF - Cancers

IS - 13

M1 - 3260

ER -

Evaluation Criteria for Chromosome Instability Detection by FISH to Predict Malignant Progression in Premalignant Glottic Laryngeal Lesions

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