E‐cadherin loss and ΔNp73L expression in oral squamous cell carcinomas showing aggressive behavior

Foschini, Maria Pia; Cocchi, R; Morandi, Luca; Marucci, Gianluca; Pennesi, Maria G.; Righi, Alberto; Tosi, Anna Lisa; Biase, Dario de; Pession, Annalisa; Montebugnoli, Lucio

doi:10.1002/hed.20908

Cited by 28 publications

(28 citation statements)

References 21 publications

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“…Several studies show positive correlation between E-cadherin expression and nodal metastasis (Tanaka et al, 2003;Bosch et al, 2005;Foschini et al, 2008;Foschini et al, 2013) but others including our study, dispute this (Mahomed et al, 2007;Lopes et al, 2009;Mostaan et al, 2011;Ukpo et al, 2012;Rosado et al, 2013). An editorial by Cerezo (2011) DOI:http://dx.doi.org/10.7314/APJCP.2014.15.5.2145 Changed Expression of E-cadherin andGalectin-9 …”

Section: Discussioncontrasting

confidence: 52%

Changed Expression of E-cadherin and Galectin-9 in Oral Squamous Cell Carcinomas but Lack of Potential as Prognostic Markers

Kallarakkal²,

Abraham³

2014

Asian Pacific Journal of Cancer Prevention

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Background: The survival rate for oral squamous cell carcinoma (OSCC) has remained generally unchanged in the past three decades, underlining the need for more biomarkers to be developed to aid prognostication and effective management. The prognostic potential of E-cadherin expression in OSCCs has been variable in previous studies while galectin-9 expression has been correlated with improved prognosis in other cancers. The aim of the present study was to investigate the expression of galectin-9 and E-cadherin in OSCC and their potential as prognostic biomarkers. Materials and Methods: E-cadherin and Galectin-9 expression was examined by immunohistochemistry in 32 cases of OSCC of the buccal mucosa (13 with and 19 without lymph node metastasis), as well as 6 samples of reactive lesions and 5 of normal buccal mucosa. Results: The expression of E-cadherin in OSCC was significantly lower than the control tissues but galectin-9 expression was conversely higher. Median E-cadherin HSCOREs between OSCCs positive and negative for nodal metastasis were not significantly different. Mean HSCOREs for galectin-9 in OSCC without lymph node metastasis (127.7±81.8) was higher than OSCC with lymph node metastasis (97.9±62.9) but this difference was not statistically significant. Conclusions: E-cadherin expression is reduced whilst galectin-9 expression is increased in OSCC. However, the present results suggest that E-cadherin and galectin-9 expression may not be useful as prognostic markers for OSCC.

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Section: Discussioncontrasting

confidence: 52%

Changed Expression of E-cadherin and Galectin-9 in Oral Squamous Cell Carcinomas but Lack of Potential as Prognostic Markers

Kallarakkal²,

Abraham³

2014

Asian Pacific Journal of Cancer Prevention

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“…Some authors propose that a low E-cadherin expression could predict lymph node metastasis in cases of human oral SCC, while others relate it to tumor differentiation. 11,13,16 Similar results were obtained in canine mammary tumors. 14,25,35 Our findings suggest that there is an association between p63 and E-cadherin expression and tumor grade.…”

Section: Discussionsupporting

confidence: 79%

p63 and E-cadherin Expression in Canine Oral Squamous Cell Carcinoma

Mestrinho¹,

Pissarra²,

Faísca

et al. 2014

Vet Pathol

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The expression of p63 and E-cadherin was studied in 22 oral squamous cell carcinomas in the dog according to immunohistochemical techniques. The association between these markers and clinicopathologic parameters was assessed. All tumor cells studied showed enhanced p63 expression. Regarding E-cadherin expression, 17 of 22 cases (77.3%) showed decreased immunoreactivity, and in 13 of 22 cases (59.1%), its expression was cytoplasmic. Neither p63 nor E-cadherin expression patterns were associated with tumor size, bone invasion, or lymph node metastasis. p63 score was related to proliferating cell nuclear antigen proliferative index (P ¼ .020). A statistically significant correlation between the expression patterns of these 2 markers was noted (P ¼ .026). Furthermore, they were related with tumor grade. An atypical p63 labeling and a cytoplasmic E-cadherin staining were statistically related with a higher tumor grade (P ¼ .022 and P ¼ .017, respectively). These findings suggest that changes in p63 and E-cadherin expression are frequent events in oral squamous cell carcinoma in dogs. Keywords p63, E-cadherin, oral squamous cell carcinoma, dogSquamous cell carcinoma (SCC) is the second-most frequent oral cancer in dogs 23 and one of the most common head and neck neoplasias in humans. 2,42 In spite of its low metastatic rate, this tumor is locally aggressive to the bone and other surrounding soft tissues. 23 Regardless of location, stage, and treatment approaches, local recurrence is very common, especially when clean surgical margins cannot be achieved.The role of p63 and E-cadherin expression in human head and neck SCC has been extensively studied, mainly with reference to their implications for prognosis. 4,12 However, there is a lack of understanding of the molecular pathogenesis underlying this cancer. 37 Substantial data indicate that both proteins play a relevant role in SCC initiation and progression. 16,29 Abnormal expression patterns of these 2 proteins have been associated with the decrease of epithelial characteristics of squamous cells and the acquisition of a mesenchymal-like phenotype.

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“…Invasive carcinomas, in addition, showed in 12 cases one of the two or both short isoforms (ΔNp73L and d4TAp63, lacking exon 4) paralleling the results obtained in salivary gland carcinomas [9] and squamous cell carcinomas of oral cavity [6,9,22] where ΔNp73L isoform was not found in normal salivary gland tissue [9] and in non-neoplastic squamous oral mucosa [6]. Moreover, the expression of ΔNp73L has been found to be associated to low expression of E-cadherin, an association predictive of development of lymph node metastases in oral squamous cell carcinomas [22].…”

Section: Discussionsupporting

confidence: 72%

p63 short isoforms are found in invasive carcinomas only and not in benign breast conditions

et al. 2010

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Two N-terminal isoforms characterize the p63 protein: the transactivating isoform TAp63 and the amino-terminal truncated isoform DeltaNp63. Two further N-terminal isoforms lacking exon 4 (d4TAp63 and DeltaNp73L) have been reported. Purpose of the study was to investigate the molecular expression of N-terminal p63 isoforms in benign and malignant breast tissues. Eighteen randomly selected cases of invasive breast carcinoma (IBC) of luminal type, two cases of in situ duct carcinoma (DCIS/DIN), and 20 specimens of normal and benign breast tissues were studied. All cases were immunostained for p63. Reverse polymerase chain reaction and nested PCR were performed to evaluate p63 N-terminal expression patterns. These isoforms whenever present were validated by sequencing. All cases of normal breast, benign lesions, and the two cases of DCIS/DIN expressed DeltaNp63 and TAp63 isoforms only. The two variants lacking exon 4 (DeltaNp73L and d4TAp63) were not found. All invasive carcinomas expressed the DeltaNp63 and TAp63 isoforms as well as the two short isoforms lacking exon 4 which were found in 11 (d4TAp63) and four (DeltaNp73L) cases. The present cases of luminal-type IBC showed p63 isoforms together with short variants lacking exon 4. These isoforms were not observed in non-neoplastic breast tissue. Presence of p63 in invasive breast carcinomas of luminal type, as seen at molecular level, suggests caution to include p63 as a marker of basal-like carcinomas.

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E‐cadherin loss and ΔNp73L expression in oral squamous cell carcinomas showing aggressive behavior

Abstract: This study shows that low E-cadherin expression is useful for predicting lymph node metastases in cases of OSCC. The predictive value is enhanced when low E-cadherin positivity is associated with DeltaNp63 and Delta Np73L expression.

Cited by 28 publications

References 21 publications

Changed Expression of E-cadherin and Galectin-9 in Oral Squamous Cell Carcinomas but Lack of Potential as Prognostic Markers

Changed Expression of E-cadherin and Galectin-9 in Oral Squamous Cell Carcinomas but Lack of Potential as Prognostic Markers

p63 and E-cadherin Expression in Canine Oral Squamous Cell Carcinoma

p63 short isoforms are found in invasive carcinomas only and not in benign breast conditions

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