Importance of tumor budding grade as independent prognostic factor for early tongue squamous cell carcinoma

Ebihara, Yasuhiro; Yoshida, Saori; Nakahira, Mitsuhiko; Kogashiwa, Yasunao; Enoki, Yuichiro; Kuba, Kiyomi; Inoue, Hitoshi; Minami, Kazuhiko; Yasuda, Masanori; Sugasawa, Masashi

doi:10.1002/hed.25614

Cited by 21 publications

(30 citation statements)

References 22 publications

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“…the correlation of NLM with TBG, but they were limited to high TBG cases (13,14). In our previous study (15), we found that TBG is the most important prognostic factor for the early T-stage tongue SCC. High TBG indicates a high risk for NLM, and is superior to DOI at predicting NLM.…”

Section: Podoplanin Is An Efficient Predictor Of Neck Lymph Node Metamentioning

confidence: 79%

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Podoplanin is an efficient predictor of neck lymph node metastasis in tongue squamous cell carcinoma with low tumor budding grade

et al. 2020

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The current study investigated the efficacy of podoplanin expression in tumor budding cells as a predictor of neck lymph node metastasis (NLM) in patients with tongue squamous cell carcinoma (SCC) of low tumor budding grade (TBG). A total of 99 patients with early T-stage tongue SCC of any clinical N status who received the initial curative treatment were enrolled. The association between podoplanin expression and NLM was immunohistochemically analyzed, with a focus on tongue SCC with low TBG. The disease-specific survival (DSS) rate was 77% at 5 years, and a significant difference was observed between the NLM-positive and NLM-negative groups, and between the low (n=77) and high (n=22) TBG groups. In the low TBG group, there was a significant difference in DSS between the NLM-positive and NLM-negative groups. The multivariate analysis showed that lymphatic vessel invasion (ly) [odds ratio (OR)=11.5, 95% confidence interval (CI): 1.50-87.6; P=0.02] and podoplanin expression (OR=7.07, 95% CI: 1.80-27.7; P=0.005) were significantly correlated with NLM. Furthermore, negative predictive values (NPV) of ly and podoplanin expression for NLM were 75% and 88%, respectively. Considering the balance of stratification case number adding to ratio, NLM-negative prediction by podoplanin was more significant than that by ly for the low TBG group. The results of the present study demonstrated that podoplanin expression in tumor budding is an independent and efficient predictor of NLM in the tongue SCC with low TBG. The low TBG and podoplanin-negative cases may be candidates for the wait and watch policy, therefore, reducing inappropriate elective neck lymph node dissections.

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Section: Podoplanin Is An Efficient Predictor Of Neck Lymph Node Metamentioning

confidence: 79%

“…Cytokeratin AE1/3-staining was useful for a less experienced pathologist (HM), as previously reported (23). The cases were divided into two groups: high TBG (TBG3) and low TBG (TBG1/2) based on previous studies (14,15).…”

Section: Methodsmentioning

confidence: 98%

Podoplanin is an efficient predictor of neck lymph node metastasis in tongue squamous cell carcinoma with low tumor budding grade

et al. 2020

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“…In OTSCC, however, there is a gap between molecular research that has already documented the importance of tumor stroma and pathology practice which has so far not included the evaluation of stromal characteristics. Currently, histopathological grading according to the WHO criteria which are based on tumor differentiation is often routinely reported in daily pathology practice, although many studies have shown that this grading has a low prognostic value for early-stage OTSCC [7,[21][22][23][24]. In addition, differences between tumors of the same type are usually assessed by evaluating tumor-related features (e.g., pattern of invasion and depth of invasion).…”

Section: Discussionmentioning

confidence: 99%

Stromal categorization in early oral tongue cancer

et al. 2020

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Stromal categorization has been used to classify many epithelial cancer types. We assessed the desmoplastic reaction and compared its significance with other stromal characteristics in early (cT1-2N0) oral tongue squamous cell carcinoma (OTSCC). In this multi-institutional study, we included 308 cases treated for early OTSCC at five Finnish university hospitals or at the A.C. Camargo Cancer Center in São Paulo, Brazil. The desmoplastic reaction was classified as immature, intermediate, or mature based on the amount of hyalinized keloid-like collagen and myxoid stroma. We compared the prognostic value of the desmoplastic reaction with a stromal grading system based on tumor-stroma ratio and stromal tumor-infiltrating lymphocytes. We found that a high amount of stroma with a weak infiltration of lymphocytes was associated statistically significantly with a worse disease-free survival with a hazard ratio (HR) of 2.68 (95% CI 1.26–5.69), worse overall survival (HR 2.95, 95% CI 1.69–5.15), and poor disease-specific survival (HR 2.66, 95% CI 1.11–6.33). Tumors having a high amount of stroma with a weak infiltration of lymphocytes were also significantly associated with a high rate of local recurrence (HR 4.13, 95% CI 1.67–10.24), but no significant association was found with lymph node metastasis (HR 1.27, 95% CI 0.37–4.35). Categorization of the stroma based on desmoplastic reaction (immature, intermediate, mature) showed a low prognostic value for early OTSCC in all survival analyses (P > 0.05). In conclusion, categorization of the stroma based on the amount of stroma and its infiltrating lymphocytes shows clinical relevance in early OTSCC superior to categorization based on the maturity of stroma.

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“…The carcinoma cell invasion budding, as detected in SiHa invasion to myoma, have independently been connected in clinical studies with deeper invasion depth, venous invasion, lymph node metastasis and poor prognosis in head-and-neck squamous cell carcinoma (HNSCC) and colorectal cancer [31][32][33][34][35][36][37][38][39][40]. Also, both in Fig.…”

Section: Discussionmentioning

confidence: 90%

Human myoma tissue-based extracellular matrix models for testing the effects of irradiation on the HPV positive cells

Tuominen

Al‐Samadi

Salo

et al. 2020

Virol J

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Background: This study was designed to investigate the invasion of human papillomavirus (HPV) positive human cervical carcinoma cell lines in human leiomyoma-based extracellular matrices in vitro, and to test the suitability of the model for studying the irradiation effects on the cancer cell invasion. Methods: HPV positive cervical carcinoma cell lines SiHa and CaSki, and HPV negative squamous cell carcinoma cell line HSC-3 were used. CaSki cells contain around 600 copies of HPV 16 virus in the genome, whereas SiHa have only 1-2 copies per cell. Cells were analyzed using two different human tumor derived extracellular matrix methods (3D myoma disc model, and Myogel Transwell invasion assay). Cultures were irradiated with 4 Gy. Myoma invasion area and the depth of invasion were measured with ImageJ 1.51j8 software. Statistical analyses were performed with SPSS Statistics (IBM SPSS® Statistics 25). Results: All cells invaded through Myogel coated Transwell membranes and within myoma discs. In myoma discs, a difference in the invasion depth (p = 0.0001) but not in invasion area (p = 0.310) between the HPV positive cell lines was seen, since SiHa (less HPV) invaded slightly better than CaSki (more HPV). HSC-3 cells (HPV negative) invaded deepest (p = 0.048) than either of the HPV positive cell line cells. No difference was detected in the invasion area (p = 0.892) between HPV positive and HPV negative cells. The ionized radiation significantly reduced the invasion depth of HSC-3 (p = 0.008), SiHa (p = 0.0001) and CaSki (p = 0.005). No significant effect on the invasion area was detected in any of the cell lines. However, a significant difference was observed between SiHa and CaSki in the reduction of the invasion depth after radiation (p = 0.013) as the reduction was greater with SiHa than CaSki. Conclusions: Both solid and gelatinous human leiomyoma-based extracellular matrix models were suitable platforms to study the invasion of HPV positive cervical carcinoma cells in vitro. SiHa cells with less HPV copy number cells invaded slightly better and were slightly more sensitive to irradiation than CaSki cells with high HPV copy number. However, there was no drastic differences between the invasion properties of these carcinoma cells.

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Importance of tumor budding grade as independent prognostic factor for early tongue squamous cell carcinoma

Cited by 21 publications

References 22 publications

Podoplanin is an efficient predictor of neck lymph node metastasis in tongue squamous cell carcinoma with low tumor budding grade

Podoplanin is an efficient predictor of neck lymph node metastasis in tongue squamous cell carcinoma with low tumor budding grade

Stromal categorization in early oral tongue cancer

Human myoma tissue-based extracellular matrix models for testing the effects of irradiation on the HPV positive cells

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