The role of neck dissection and postoperative adjuvant radiotherapy in cN0 patients with PNI-positive squamous cell carcinoma of the oral cavity

Chatzistefanou, Ioannis; Lubek, Joshua E.; Markou, Konstantinos; Ord, Robert A.

doi:10.1016/j.oraloncology.2014.05.005

Cited by 63 publications

(71 citation statements)

References 88 publications

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“…5C, 5I) (Alexander et al 2013;Friedl and Alexander 2011). Perineural invasion is a feature that is also observed in malignant squamous cell carcinomas of, for example, the esophagus , skin (Adams et al 2014), tongue (Shen et al 2014) and oral cavity (Chatzistefanou et al 2014).…”

Section: Discussionmentioning

confidence: 97%

Expression of the Ly6/uPAR-Domain Proteins C4.4A and Haldisin in Non-Invasive and Invasive Skin Lesions

Kriegbaum

Clausen

Lærum

et al. 2014

J Histochem Cytochem.

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C4.4A and Haldisin belong to the Ly6/uPAR/α-neurotoxin protein domain family. They exhibit highly regulated expression profiles in normal epidermis, where they are confined to early (C4.4A) and late (Haldisin) squamous differentiation. We have now explored if dysregulated expressions occur in non-invasive and invasive skin lesions. In non-invasive lesions, their expression signatures were largely maintained as defined by that of normal epidermis. The scenario was, however, markedly different in the progression towards invasive squamous cell carcinomas. In its non-invasive stage (carcinoma in situ), a pronounced attenuation of C4.4A expression was observed, but upon transition to malignant invasive squamous cell carcinomas, the invasive fronts regained high expression of C4.4A. A similar progression was observed for the early stages of benign infiltrating keratoacanthomas. Interestingly, this transition was accompanied by a shift in the predominant association of C4.4A expression with CK1/10 in the normal epidermis to CK5/14 in the invasive lesions. In contrast, Haldisin expression maintained its confinement to the most-differentiated cells and was hardly expressed in the invasive lesions. Because this altered expression of C4.4A was seen in the invasive front of benign (keratoacanthomas) and malignant (squamous cell carcinomas) neoplasms, we propose that this transition of expression is primarily related to the invasive process.

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Section: Discussionmentioning

confidence: 97%

Expression of the Ly6/uPAR-Domain Proteins C4.4A and Haldisin in Non-Invasive and Invasive Skin Lesions

Kriegbaum

Clausen

Lærum

et al. 2014

J Histochem Cytochem.

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“…This may contribute to the contradictory conclusions reached by different authors regarding the prognostic value of PNI in HNSCC. Although some authors have concluded that PNI is an independent predictor of regional recurrence, others have found no association . The wide range of incidence of PNI reported in the literature also reflects the lack of a standardized definition of PNI .…”

Section: Discussionmentioning

confidence: 99%

“…One of the limitations of the existing literature pertaining to PNI is the lack of a standardized definition of or method for detecting PNI . Liebig et al proposed the most widely cited definition of PNI, according to which PNI is present when tumor cells are identified in any of the 3 layers of the nerve sheath or tumor is identified in close proximity to the nerve and involves more than one‐third of its circumference. However, other authors have defined PNI more broadly as tumor cells touching a nerve .…”

Section: Discussionmentioning

confidence: 99%

“…Perineural invasion (PNI), the histologic finding of nerve invasion by tumor cells, is generally accepted as a poor prognostic factor in head and neck squamous cell carcinoma (HNSCC) and has been associated with increased locoregional recurrence and decreased survival . PNI has also been shown to predict concurrent cervical lymph node metastasis, an important negative prognostic factor in early oral cavity cancer . However, the optimal treatment regimen for patients with early head and neck cancer with PNI remains a topic of significant debate …”

Section: Introductionmentioning

confidence: 99%

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Adjuvant radiotherapy for early head and neck squamous cell carcinoma with perineural invasion: A systematic review

2015

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Perineural invasion (PNI) is widely regarded as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Treatment guidelines recommend adjuvant radiotherapy (RT) for patients with adverse pathologic features, including PNI. The purpose of this study was to systematically review the literature to determine if patients with PNI as their only indication for adjuvant therapy benefit from adjuvant RT. In total, 339 abstracts were reviewed for relevance leaving 85 articles, which were evaluated in detail. Thirteen retrospective studies addressed the role of adjuvant RT for patients with PNI. Evidence is lacking to recommend adjuvant RT for all patients with HNSCC with PNI. However, the literature suggests that large nerve or multifocal PNI may predict worse outcome and may be a more appropriate indication for adjuvant therapy. We advocate that patients decide whether to undergo adjuvant therapy after a discussion of the limitations of current evidence. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2350-E2357, 2016.

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“…This study adopted pathologic criteria for PNI that was congruent with those of Liebig et al, including tumor cells in any layer of the nerve sheath and/or tumor involving more than a third of a nerve's circumference. Their analysis revealed that, despite PNI(+) OCSCC having a higher rate of regional lymph node spread and regional recurrence warranting a neck dissection, adjuvant radiation therapy did not significantly reduce the incidence of local recurrence ( P = 0.763, odds ratio [OR] = 3.387) or regional recurrence ( P = 0.319, OR 4.741) …”

Section: Literature Reviewmentioning

confidence: 99%

What additional treatment is indicated for oral cavity cancer with isolated perineural invasion?

2017

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The role of neck dissection and postoperative adjuvant radiotherapy in cN0 patients with PNI-positive squamous cell carcinoma of the oral cavity

Cited by 63 publications

References 88 publications

Expression of the Ly6/uPAR-Domain Proteins C4.4A and Haldisin in Non-Invasive and Invasive Skin Lesions

Expression of the Ly6/uPAR-Domain Proteins C4.4A and Haldisin in Non-Invasive and Invasive Skin Lesions

Adjuvant radiotherapy for early head and neck squamous cell carcinoma with perineural invasion: A systematic review

What additional treatment is indicated for oral cavity cancer with isolated perineural invasion?

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