Immunohistochemical assessment of growth factor signaling molecules: MAPK, Akt, and STAT3 pathways in oral epithelial precursor lesions and squamous cell carcinoma

Tashiro, Kazuki; Oikawa, Masahiro; Miki, Yasuhiro; Takahashi, Tsuneo; Kumamoto, Hiroyuki

doi:10.1007/s10266-019-00428-4

Cited by 19 publications

(12 citation statements)

References 37 publications

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“…Since oral squamous cell carcinomas (OSCC) typically originates from non-aberrant keratinocytes which are chronically exposed to a toxic stimulus leading to dysplasia followed by invasive growth of carcinomatous cells, carcinogenesis consists of a smooth transition that is sometimes hard to detect or to differentiate from benign lesions [7]. Latest studies could show that increased levels of interleukin-8, subcutaneous adipose tissue and pSTAT3 can be found in patients with OSCC [7,15]. Baran et al found an association between the melanoma-associated antigens A family and a high risk for malignant transformation of leukoplakia [16].…”

Section: Introductionmentioning

confidence: 99%

Consequences of the COVID-19 Pandemic and Governmental Containment Policies on the Detection and Therapy of Oral Malignant Lesions—A Retrospective, Multicenter Cohort Study from Germany

Heimes

Müller

Schellin

et al. 2021

Cancers

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(1) Background: In response to the global COVID-19 pandemic, governmental measures have been undertaken. The impact of the crisis on the healthcare of patients with cancer is largely unexplored. This multicenter cohort study aimed to investigate a potential screening delay and its consequences in patients with oral cancer (OC) during the pandemic. (2) Material and Methods: Data of patients who were first diagnosed with OC during different periods were collected, especially in terms of OC incidence, tumor stage/entity and time to intervention. The periods lockdown (LD) (13 March–16 June 2020), post-lockdown (PLD) (17 June–1 November 2020), and the corresponding equivalents in 2018/19 were differentiated and compared. (3) Results: There was no obvious trend towards a higher incidence of OC or higher tumor stages, whereas a trend towards a shorter time to intervention during the LD2020 could be observed. Subgroup analyses revealed an increased incidence in OC within the PLD2020 in Mainz, which might be explained by the partial closure of dental practices in this federal state during LD. (4) Conclusions: While there was no overall higher incidence of OC, we found closure of practices during LD to possibly delay cancer diagnosis. Therefore, measures must be taken to identify patients at risk and to ensure basic healthcare, especially in the context of dental screening measures.

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Section: Introductionmentioning

confidence: 99%

Consequences of the COVID-19 Pandemic and Governmental Containment Policies on the Detection and Therapy of Oral Malignant Lesions—A Retrospective, Multicenter Cohort Study from Germany

Heimes

Müller

Schellin

et al. 2021

Cancers

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“…Kazuki et al reported that pAkt tended to increase with low differentiation and deep invasion in oral cancer. 34 These features suggested that pAkt, pmTOR and p4E-BP1 might correlate with low differentiation and could be prognostic factors. The univariate prognostic factor p4E-BP1 was correlated with a larger size and a larger extent of necrosis.…”

Section: Discussionmentioning

confidence: 98%

“…Kazuki et al showed that pAkt and pmTOR were localised to the nuclei and cytoplasm of epithelial or carcinoma cells in oral squamous cell carcinoma. 34 EWA et al observed concurrent cytoplasmic and nuclear pmTOR expression in neuroblastoma and p4E-BP1 in most cases of neuroblastoma in the cytoplasm and often within the nucleus. 21 In addition, we found that much stronger staining in nuclei than in cytoplasm of epithelioid tumour cells was observed in the biphasic SS tumours.…”

Section: Discussionmentioning

confidence: 98%

<p>Impact of the Activation Status of the Akt/mTOR Signalling Pathway on the Clinical Behaviour of Synovial Sarcoma: Retrospective Analysis of 174 Patients at a Single Institution</p>

Li¹,

Ding²,

Wen³

et al. 2020

CMAR

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Phosphoinositide 3-kinase (PI3K) and the downstream Akt/mammalian target of rapamycin (mTOR) pathway are central to the control of cell proliferation and survival. Although abnormal activation of this pathway has been well established in a variety of tumours, limited studies are available on synovial sarcoma. The aim of this study was to investigate the expression of several key proteins of those pathways in synovial sarcomas and to correlate the expression of these proteins with clinicopathologic features and prognosis. Patients and Methods: A total of 174 patients with synovial sarcomas were recruited for this study. The phosphorylation status of Akt, mTOR, and eukaryotic translation initiation factor 4E binding protein (4E-BP1) was measured by immunohistochemistry assays in formalin-fixed, paraffin-embedded samples. Correlations between the expression levels of these proteins and clinicopathologic features and prognosis were analysed. Results: The positive rates of phosphorylated (p)Akt, pmTOR, p4E-BP1, and CyclinD1 were 62.7%, 55.6%, 47.1%, and 52.6%, respectively. The positive results of pmTOR, pAkt, and downstream p4E-BP1 were correlated with each other. The positive pAkt, pmTOR, p4E-BP1, and CyclinD1 results were more highly expressed in head and neck and visceral tumours, and positive p4E-BP1 results were correlated with larger size and larger areas of necrosis. In multivariate analysis of clinicopathologic factors, head and neck and visceral location, large tumour size, larger areas of necrosis and frequent mitosis were confirmed as risk factors for shorter overall survival. Positive pAkt, pmTOR and p4E-BP1 results were correlated significantly with shorter overall survival, and CyclinD1 was not in the univariate analysis. The positive pmTOR, pAkt, p4E-BP1, and CyclinD1 results were significantly poor prognostic factors for overall survival, and only positive p4E-BP1 results were significantly associated with shorter event-free survival in multivariate analysis. Conclusion: This study demonstrated the high expression of pAkt, pmTOR, and p4E-BP1 associated with aggressive clinical behaviour in synovial sarcomas and provided evidence for prognostic evaluation and targeted therapy.

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“…STAT3 has been characterized as an oncogenic molecule, which is activated by different upstream events, conveys messages to the nucleus and drives the transcription of molecules promoting cell proliferation (such as cyclin D1 and other regulators of the cell cycle) [ 40 ] and inhibiting apoptosis (such as Bcl-xL and survivin) [ 20 , 41 ]. STAT3 aberrant expression has been associated with poor clinical outcome in OSCC [ 42 , 43 , 44 ]. In addition, it has been demonstrated that dysplastic lesions are characterized by increased STAT3 expression levels [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Recurrence in Oral Premalignancy: Clinicopathologic and Immunohistochemical Analysis

et al. 2021

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Oral leukoplakia (OL) has a propensity for recurrence and malignant transformation (MT). Herein, we evaluate sociodemographic, clinical, microscopic and immunohistochemical parameters as predictive factors for OL recurrence, also comparing primary lesions (PLs) with recurrences. Thirty-three patients with OL, completely removed either by excisional biopsy or by laser ablation following incisional biopsy, were studied. Selected molecules associated with the STAT3 oncogenic pathway, including pSTAT3, Bcl-xL, survivin, cyclin D1 and Ki-67, were further analyzed. A total of 135 OL lesions, including 97 PLs and 38 recurrences, were included. Out of 97 PLs, 31 recurred at least once and none of them underwent MT, during a mean follow-up time of 48.3 months. There was no statistically significant difference among the various parameters in recurrent vs. non-recurrent PLs, although recurrence was most frequent in non-homogeneous lesions (p = 0.087) and dysplastic lesions recurred at a higher percentage compared to hyperplastic lesions (34.5% vs. 15.4%). Lower levels of Bcl-xL and survivin were identified as significant risk factors for OL recurrence. Recurrences, although smaller and more frequently homogeneous and non-dysplastic compared to their corresponding PLs, exhibited increased immunohistochemical expression of oncogenic molecules, especially pSTAT3 and Bcl-xL. Our results suggest that parameters associated with recurrence may differ from those that affect the risk of progression to malignancy and support OL management protocols favoring excision and close monitoring of all lesions.

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Immunohistochemical assessment of growth factor signaling molecules: MAPK, Akt, and STAT3 pathways in oral epithelial precursor lesions and squamous cell carcinoma

Cited by 19 publications

References 37 publications

Consequences of the COVID-19 Pandemic and Governmental Containment Policies on the Detection and Therapy of Oral Malignant Lesions—A Retrospective, Multicenter Cohort Study from Germany

Consequences of the COVID-19 Pandemic and Governmental Containment Policies on the Detection and Therapy of Oral Malignant Lesions—A Retrospective, Multicenter Cohort Study from Germany

<p>Impact of the Activation Status of the Akt/mTOR Signalling Pathway on the Clinical Behaviour of Synovial Sarcoma: Retrospective Analysis of 174 Patients at a Single Institution</p>

Recurrence in Oral Premalignancy: Clinicopathologic and Immunohistochemical Analysis

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