High expression of class III β-tubulin in small cell lung carcinoma

Abstract

Class III β-tubulin (TUBB3) is emerging as a biomarker in a number of cancers. TUBB3 has been shown to be a prognostic indicator of more aggressive disease and a predictor of resistance to taxanes and vinca alkaloids. To date, there is little data on TUBB3 expression in small cell lung carcinoma (SCLC). The primary objective of this study was to determine the expression of TUBB3 in SCLC. Immunohistochemical staining of SCLC tumor specimens was performed using standard procedures. Expression of TUBB3 was determined as a composite of the percentage of malignant cells staining positive and the intensity of staining. Clinical and tumor data for each patient was compared with the degree of TUBB3 expression. A total of 66 SCLCs were evaluable for TUBB3 expression. The majority of specimens (n=56, 85%) had high expression of TUBB3. Only 4.5% (n=3) had low expression of TUBB3. The mean distribution of positive staining for the specimens was 87.3±1.8% (mean ± SE). Specimens from core biopsies were significantly more likely to have high TUBB3 expression when compared with fine needle aspirates (P=0.004). There were no other significant findings when comparing clinical or tumor characteristics. Overall, we found that expression of TUBB3 in SCLC is higher than expected. Innate resistance to microtubule inhibitors, such as the taxanes and vinca alkaloids, may be associated with this finding. Attempts at microtubule inhibition with novel agents may be able to overcome this resistance mechanism. Further evaluation of TUBB3 as a biomarker in SCLC is warranted.

βIII-Tubulin Regulates Breast Cancer Metastases to the Brain

“…Overexpression of TUBB3 is associated with poor prognosis of multiple epithelial malignancies including lung, colorectal and ovarian cancers (16–20). Moreover, 85% of small cell lung cancer (SCLC) patients exhibit TUBB3 overexpression (27), a cohort of which shows the highest incidence of CNS metastasis (28). These reports support the notion that TUBB3 overexpression imparts metastatic potential to cancer cells.…”

Prevalence of βIII-tubulin (TUBB3) expression in human normal tissues and cancers

“…16 As the number of studies suggesting biological and clinical relevance of βIII-tubulin is rapidly increasing, there are also a growing number of reports showing considerable discrepancies with respect to the frequency of expression in various cancer types. For example, reported frequencies on βΙΙΙ-tubulin expression ranges from 17% to 85% in non–small cell lung cancer, 17,18 from 20% to 67% in serous ovary cancer, 15,19 from 10% to 100% in colon adenocarcinoma, 5 and from 12% to 100% in prostate cancer. 19,20 These discrepancies are obviously due to the use of different antibodies and staining protocols in these studies.…”

“…Figure 2.Percentage of TUBB3 cancers in previous studies (blue dots) as compared to the results of our study (red dots). Figures[1],29 [2],4 [3],30 [4],31,32 [5],32,33 [6],33 [7],5,12,18,[34][35][36][37][38][39][40][41][42] [8],19 [9],19 [10],15 [12],15 [13],15 [14],15,19,43 [15],44 [16],19,31 [17],45,46 [18],19 [19],5,19,[47][48][49] [20],50…”

Expression of Class III Beta-tubulin Predicts Prognosis in Patients with Cisplatin-resistant Bladder Cancer Receiving Paclitaxel-based Second-line Chemotherapy

“…We cannot explain the reason for the discrepancy between UC and other malignancies regarding the pathological significance of TUBB3. However, several other studies on a variety of malignancies have also repeated that TUBB3 expression is not associated with stage or metastatic status (7,(26)(27)(28). Finally, we speculate that methodological differences, such as antibodies used, method of evaluation, and background of patients, may contribute to this discrepancy, and that the pathological roles of TUBB3 in invasion and metastasis are minimal in UC.…”