Redefining Perineural Invasion: Integration of Biology With Clinical Outcome
A diagnosis of perineural invasion (PNI), defined as cancer within or surrounding at least 33% of the nerve, leads to selection of aggressive treatment in squamous cell carcinoma (SCC). Recent mechanistic studies show that cancer and nerves interact prior to physical contact. The purpose of this stu...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-07-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558618301155 |
| _version_ | 1811278867584778240 |
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| author | Ligia B. Schmitd Lauren J. Beesley Nickole Russo Emily L. Bellile Ronald C. Inglehart Min Liu Genevieve Romanowicz Gregory T. Wolf Jeremy M.G. Taylor Nisha J. D'Silva |
| author_facet | Ligia B. Schmitd Lauren J. Beesley Nickole Russo Emily L. Bellile Ronald C. Inglehart Min Liu Genevieve Romanowicz Gregory T. Wolf Jeremy M.G. Taylor Nisha J. D'Silva |
| author_sort | Ligia B. Schmitd |
| collection | DOAJ |
| description | A diagnosis of perineural invasion (PNI), defined as cancer within or surrounding at least 33% of the nerve, leads to selection of aggressive treatment in squamous cell carcinoma (SCC). Recent mechanistic studies show that cancer and nerves interact prior to physical contact. The purpose of this study was to explore cancer-nerve interactions relative to clinical outcome. Biopsy specimens from 71 patients with oral cavity SCC were stained with hematoxylin and eosin and immunohistochemical (IHC; cytokeratin, S100, GAP43, Tuj1) stains. Using current criteria, PNI detection was increased with IHC. Overall survival (OS) tended to be poor for patients with PNI (P = .098). OS was significantly lower for patients with minimum tumor-nerve distance smaller than 5 μm (P = .011). The estimated relative death rate decreased as the nerve-tumor distance increased; there was a gradual drop off in death rate from distance equal to zero that stabilized around 500 μm. In PNI-negative patients, nerve diameter was significantly related to OS (HR 2.88, 95%CI[1.11,7.49]). Among PNI-negative nerves, larger nerve-tumor distance and smaller nerve diameter were significantly related to better OS, even when adjusting for T-stage and age (HR 0.82, 95% CI[0.72,0.92]; HR 1.27, 95% CI[1.00,1.62], respectively). GAP43, a marker for neuronal outgrowth, stained less than Tuj1 in nerves at greater distances from tumor (OR 0.76, 95% CI[0.73,0.79]); more GAP43 staining was associated with PNI. Findings from a small group of patients suggest that nerve parameters other than presence of PNI can influence outcome and that current criteria of PNI need to be re-evaluated to integrate recent biological discoveries. |
| first_indexed | 2024-04-13T00:44:25Z |
| format | Article |
| id | doaj.art-612154c3c7214527af1727d368270ea3 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 |
| language | English |
| last_indexed | 2024-04-13T00:44:25Z |
| publishDate | 2018-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-612154c3c7214527af1727d368270ea32022-12-22T03:10:04ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55862018-07-01207657667Redefining Perineural Invasion: Integration of Biology With Clinical OutcomeLigia B. Schmitd0Lauren J. Beesley1Nickole Russo2Emily L. Bellile3Ronald C. Inglehart4Min Liu5Genevieve Romanowicz6Gregory T. Wolf7Jeremy M.G. Taylor8Nisha J. D'Silva9Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA;Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, USAPeriodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA;Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, USAPeriodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA;Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA;Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA;Otolaryngology, University of Michigan Medical School, 1500 E Medical Center Dr, Ann Arbor, MI, USABiostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, USAPeriodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 N. University Ave, Ann Arbor, MI, USA;; Pathology, University of Michigan Medical School, 1500 E Medical Center Dr, Ann Arbor, MI, USA; Address all correspondence to: Nisha J D'Silva, Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry, 1011 North University Ave, Room G018, Ann Arbor, MI 48109-1078, USA.A diagnosis of perineural invasion (PNI), defined as cancer within or surrounding at least 33% of the nerve, leads to selection of aggressive treatment in squamous cell carcinoma (SCC). Recent mechanistic studies show that cancer and nerves interact prior to physical contact. The purpose of this study was to explore cancer-nerve interactions relative to clinical outcome. Biopsy specimens from 71 patients with oral cavity SCC were stained with hematoxylin and eosin and immunohistochemical (IHC; cytokeratin, S100, GAP43, Tuj1) stains. Using current criteria, PNI detection was increased with IHC. Overall survival (OS) tended to be poor for patients with PNI (P = .098). OS was significantly lower for patients with minimum tumor-nerve distance smaller than 5 μm (P = .011). The estimated relative death rate decreased as the nerve-tumor distance increased; there was a gradual drop off in death rate from distance equal to zero that stabilized around 500 μm. In PNI-negative patients, nerve diameter was significantly related to OS (HR 2.88, 95%CI[1.11,7.49]). Among PNI-negative nerves, larger nerve-tumor distance and smaller nerve diameter were significantly related to better OS, even when adjusting for T-stage and age (HR 0.82, 95% CI[0.72,0.92]; HR 1.27, 95% CI[1.00,1.62], respectively). GAP43, a marker for neuronal outgrowth, stained less than Tuj1 in nerves at greater distances from tumor (OR 0.76, 95% CI[0.73,0.79]); more GAP43 staining was associated with PNI. Findings from a small group of patients suggest that nerve parameters other than presence of PNI can influence outcome and that current criteria of PNI need to be re-evaluated to integrate recent biological discoveries.http://www.sciencedirect.com/science/article/pii/S1476558618301155 |
| spellingShingle | Ligia B. Schmitd Lauren J. Beesley Nickole Russo Emily L. Bellile Ronald C. Inglehart Min Liu Genevieve Romanowicz Gregory T. Wolf Jeremy M.G. Taylor Nisha J. D'Silva Redefining Perineural Invasion: Integration of Biology With Clinical Outcome Neoplasia: An International Journal for Oncology Research |
| title | Redefining Perineural Invasion: Integration of Biology With Clinical Outcome |
| title_full | Redefining Perineural Invasion: Integration of Biology With Clinical Outcome |
| title_fullStr | Redefining Perineural Invasion: Integration of Biology With Clinical Outcome |
| title_full_unstemmed | Redefining Perineural Invasion: Integration of Biology With Clinical Outcome |
| title_short | Redefining Perineural Invasion: Integration of Biology With Clinical Outcome |
| title_sort | redefining perineural invasion integration of biology with clinical outcome |
| url | http://www.sciencedirect.com/science/article/pii/S1476558618301155 |
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