0
Study |

Pronounced Allelic Imbalance at D9S162 in Skin Squamous Cell Carcinoma of Organ Transplant Recipients

Beda Mühleisen, MD; Ivaylo Petrov, MD; Simona Frigerio, MD; Piotr Dziunycz, MD; Lars E. French, MD; Günther F. L. Hofbauer, MD
Arch Dermatol. 2012;148(6):697-703. doi:10.1001/archdermatol.2012.107.
Text Size: A A A
Published online

Objective  To evaluate chromosomal instability at 9p21-22 with p16 protein expression in organ transplant recipients (OTRs) compared with immunocompetent patients with squamous cell carcinoma (SCC).

Design  In a select population of intraepithelial and subsequent invasive SCC from the same anatomic region of the same patient at different times, we assessed loss of heterozygosity at 3 microsatellites—IFNA, D9S162, and D9S925—in the course of carcinogenesis in OTRs and immunocompetent patients.

Setting  Department of Dermatology, University Hospital Zurich.

Patients  Immunocompetent patients and OTRs with SCC on sun-damaged skin.

Main Outcome Measure  Chromosomal allelic balance in SCC of OTRs and immunocompetent patients.

Results  Reduced allelic balance at IFNA, D9S162, and D9S925 in intraepithelial forms of SCC and similar allelic imbalance in invasive forms of SCC were found. Allelic balance at D9S162 was reduced for SCC in OTRs compared with SCC in immunocompetent patients. The study revealed broadly reduced allelic balance at 9p21-22 in all cutaneous SCCs, and OTRs presented a further reduced allelic balance for D9S162, suggesting a common trait for SCC in OTRs. Actinic keratosis and Bowen disease differed in allelic balance at D9S162, suggesting substantial differences in their carcinogenesis.

Conclusion  Reduced allelic balance around locus D9S162 is a genomic correlate for enhanced carcinogenesis in OTRs.

Figures in this Article

Sign In to Access Full Content

Don't have Access?

Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more

Subscribe for full-text access to content from 1998 forward and a host of useful features

Activate your current subscription (AMA members and current subscribers)

Purchase Online Access to this article for 24 hours

Figures

Place holder to copy figure label and caption
Grahic Jump Location

Figure 1. Allelic balance ratios for squamous cell carcinoma (SCC) in immunocompetent patients (ICPs) and organ transplant recipients (OTRs). A, Allelic balance was similarly reduced in all SCC (intraepithelial and invasive) samples. Two-tailed P values were determined with Wilcoxon matched-pairs test. Total number of patients, 80. IFNA informative paired samples, 20 (P = .56); D9S162 informative paired samples, 29 (P = .47); and D9S925 informative paired samples, 31 (P = .58). B, Squamous cell carcinoma in OTRs overall showed reduced allelic balance for D9S162 vs SCC in ICPs. Two-tailed P values were determined with the Mann-Whitney test. Total number of SCC samples, 170. IFNA informative samples: ICPs, 42; OTRs, 31 (P = .35). D9S162 informative samples: ICP, 49; OTRs, 37 (P = .04). D9S925 informative samples: ICPs, 49; OTRs, 46 (P = .21). Two-tailed P values were determined with Wilcoxon matched-pairs test. The horizontal line in the middle of each box indicates the median, while the top and bottom borders of the box mark the 75th and 25th percentiles. The whiskers represent the 95th and 9th percentiles.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 2. Allelic balance ratios in actinic keratosis (AK) and Bowen disease (BD). A, Overall, AK showed reduced allelic balance for D9S162 compared with BD. Bowen disease showed significantly higher allelic balance at D9S162 compared with AK (P = .004). IFNA informative samples: AK, 30; BD, 10. D9S162 informative samples: AK, 32; BD, 11. D9S925 informative samples: AK, 31; BD, 14. Two-tailed P values were determined with the Mann-Whitney test. Total number of AK, 63; BD, 22. B, Actinic keratosis in organ transplant recipients (OTRs) showed less allelic balance for D9S162 than BD in OTRs (P = .01; Mann-Whitney test). IFNA informative samples: AK, 12; BD, 5. D9S162 informative samples: AK, 13; BD, 7. D9S925 informative samples: AK, 13; BD, 10. Total number of intraepithelial squamous cell carcinoma (SCC) samples in OTRs: AK, 29; BD, 13. P values were determined with the Fisher exact test. The box and whisker plot elements are defined in the legend to Figure 1. C, AK in OTRs expressed less p16 protein than did BD in OTRs (P < .005; analysis of variance). The numbers on the x-axis represent the proportion of p16 immunoreactive tumor cells grouped by percentage of immunoreactive cells within the tumors. ICPs indicates immunocompetent patients; NS, nonsignificant.

Place holder to copy figure label and caption
Grahic Jump Location

Figure 3. Allelic balance ratios of invasive squamous cell carcinoma (SCC) in immunocompetent patients (ICPs) and organ transplant recipients (OTRs). A, Invasive SCC in OTRs shows reduced allelic balance for D9S162 compared with invasive SCC in ICPs (P = .048; 2-tailed P value was determined with the Mann-Whitney test). IFNA informative samples: ICPs, 19; OTRs, 14. D9S162 informative samples: ICPs, 26; OTRs, 17. D9S925 informative samples: ICPs, 27; OTRs, 23. Total number of invasive SCC samples, 85. The box and whisker plot elements are defined in the legend to Figure 1. B, Invasive SCC of OTRs expressed more p16 protein than invasive SCC of immunocompetent patients (P < .001; analysis of variance). The numbers on the x-axis represent the proportions of p16 immunoreactive tumor cells in intraepithelial and invasive SCC in ICPs and OTRs grouped by the percentage of immunoreactive cells within the tumors.

Tables

Interactive Graphics

Video

Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

References

Correspondence

CME
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s “Cited By” API will populate this tab (http://www.crossref.org/citedby.html).
Submit a Comment

Some tools below are only available to our subscribers or users with an online account.

Sign In to Access Full Content

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Jobs