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Giancarlo Marra
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Background: Approximately 60% of colorectal cancer (CRC) precursor lesions are the genuinely-dysplastic conventional adenomas (cADNs). The others include hyperplastic polyps (HPs), sessile serrated adenoma/polyps (SSA/Ps), and traditional serrated adenomas (TSAs), subtypes of a class of lesions collectively referred to as “serrated.” Endoscopic and histologic differentiation between cADNs and serrated lesions, and between serrated lesion subtypes can be difficult.
Methods: We used in situ hybridization to verify the expression patterns in CRC precursors of 21 RNA molecules that appear to be promising differentiation markers on the basis of previous RNA sequencing studies.
Results: SSA/Ps could be clearly differentiated from cADNs by the expression patterns of 9 of the 12 RNAs tested for this purpose (VSIG1, ANXA10, ACHE, SEMG1, AQP5, LINC00520, ZIC5/2, FOXD1, NKD1). Expression patterns of all 9 in HPs were similar to those in SSA/Ps. Nine putatively HP-specific RNAs were also investigated, but none could be confirmed as such: most (e.g., HOXD13 and HOXB13), proved instead to be markers of the normal mucosa in the distal colon and rectum, where most HPs arise. TSAs displayed mixed staining patterns reflecting the presence of serrated and dysplastic glands in the same lesion.
Conclusions: Using a robust in situ hybridization protocol, we identified promising tissue-staining markers that, if validated in larger series of lesions, could facilitate more precise histologic classification of CRC precursors and, consequently, more tailored clinical follow-up of their carriers. Our findings should also fuel functional studies on the pathogenic significance of specific gene expression alterations in the initiation and evolution of CRC precursor subtypes.
Keywords
Sessile serrated adenoma/polyp, hyperplastic polyp, traditional serrated adenoma, adenomatous polyp, colorectal cancer, gene expression, in situ hybridization, tissue staining markers
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Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- FullResolutionFigures.zip
- SupplementaryFigure1.pdf
- SupplementaryFigure2.pdf
- SupplementaryFigure3.pdf
- SupplementaryFigure4.pdf
- SupplementaryFigure5.pdf
- SupplementaryFigure6.pdf
- SupplementaryFigure7.pdf
- SupplementaryFigure8.pdf
- SupplementaryFigure9.pdf
- SupplementaryFigure10.pdf
- SupplementaryFigure11.pdf
- SupplementaryFigure12.pdf
- SupplementaryFigure13.pdf
- SupplementaryFigure14.pdf
- SupplementaryFigure15.pdf
- SupplementaryFigure16.pdf
- SupplementaryFigure17.pdf
- SupplementaryTable1.pdf
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CURRENT STATUS: Published
View the published article at Diagnostic Pathology.
No community comments so far
Editorial decision: Accept
On 26 Dec, 2020
Review #1 received
Received 02 Dec, 2020
Reviewer #1 agreed
On 01 Dec, 2020
Reviewers invited
Invitations sent on 26 Nov, 2020
Editor assigned
On 17 Nov, 2020
Submission checks complete
On 17 Nov, 2020
Editor invited
On 17 Nov, 2020
Version 1
Posted 23 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 02 Nov, 2020
Reviewer #1 agreed
On 22 Aug, 2020
Review #1 received
Received 22 Aug, 2020
Reviewers invited
Invitations sent on 18 Aug, 2020
Editor assigned
On 07 Aug, 2020
Editor invited
On 06 Aug, 2020
Submission checks complete
On 22 Jul, 2020
First submitted
On 17 Jul, 2020
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Subject Areas
Pathology
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A new preprint design is coming!
We have improved readability, clarity, accessibility, and opportunities for engagement.
See the published version of this preprint at Diagnostic Pathology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Giancarlo Marra
Corresponding Author
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at Diagnostic Pathology.
No community comments so far
Editorial decision: Accept
On 26 Dec, 2020
Review #1 received
Received 02 Dec, 2020
Reviewer #1 agreed
On 01 Dec, 2020
Reviewers invited
Invitations sent on 26 Nov, 2020
Editor assigned
On 17 Nov, 2020
Submission checks complete
On 17 Nov, 2020
Editor invited
On 17 Nov, 2020
Version 1
Posted 23 Jul, 2020
No comments provided
Editorial decision: Major Revision
On 02 Nov, 2020
Reviewer #1 agreed
On 22 Aug, 2020
Review #1 received
Received 22 Aug, 2020
Reviewers invited
Invitations sent on 18 Aug, 2020
Editor assigned
On 07 Aug, 2020
Editor invited
On 06 Aug, 2020
Submission checks complete
On 22 Jul, 2020
First submitted
On 17 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pathology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at Diagnostic Pathology.
Background: Approximately 60% of colorectal cancer (CRC) precursor lesions are the genuinely-dysplastic conventional adenomas (cADNs). The others include hyperplastic polyps (HPs), sessile serrated adenoma/polyps (SSA/Ps), and traditional serrated adenomas (TSAs), subtypes of a class of lesions collectively referred to as “serrated.” Endoscopic and histologic differentiation between cADNs and serrated lesions, and between serrated lesion subtypes can be difficult.
Methods: We used in situ hybridization to verify the expression patterns in CRC precursors of 21 RNA molecules that appear to be promising differentiation markers on the basis of previous RNA sequencing studies.
Results: SSA/Ps could be clearly differentiated from cADNs by the expression patterns of 9 of the 12 RNAs tested for this purpose (VSIG1, ANXA10, ACHE, SEMG1, AQP5, LINC00520, ZIC5/2, FOXD1, NKD1). Expression patterns of all 9 in HPs were similar to those in SSA/Ps. Nine putatively HP-specific RNAs were also investigated, but none could be confirmed as such: most (e.g., HOXD13 and HOXB13), proved instead to be markers of the normal mucosa in the distal colon and rectum, where most HPs arise. TSAs displayed mixed staining patterns reflecting the presence of serrated and dysplastic glands in the same lesion.
Conclusions: Using a robust in situ hybridization protocol, we identified promising tissue-staining markers that, if validated in larger series of lesions, could facilitate more precise histologic classification of CRC precursors and, consequently, more tailored clinical follow-up of their carriers. Our findings should also fuel functional studies on the pathogenic significance of specific gene expression alterations in the initiation and evolution of CRC precursor subtypes.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
This is a list of supplementary files associated with this preprint. Click to download.
- FullResolutionFigures.zip
- SupplementaryFigure1.pdf
- SupplementaryFigure2.pdf
- SupplementaryFigure3.pdf
- SupplementaryFigure4.pdf
- SupplementaryFigure5.pdf
- SupplementaryFigure6.pdf
- SupplementaryFigure7.pdf
- SupplementaryFigure8.pdf
- SupplementaryFigure9.pdf
- SupplementaryFigure10.pdf
- SupplementaryFigure11.pdf
- SupplementaryFigure12.pdf
- SupplementaryFigure13.pdf
- SupplementaryFigure14.pdf
- SupplementaryFigure15.pdf
- SupplementaryFigure16.pdf
- SupplementaryFigure17.pdf
- SupplementaryTable1.pdf
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