MUC4 and MUC1 expression in adenocarcinoma of the stomach correlates with vessel invasion and lymph node metastasis: an immunohistochemical study of early gastric cancer.

We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by Western blotting and IHC of two MUC4 mRNA expressing gastric cancer cell lines. MAb 8G7 reacted clearly, whereas MAb 1G8 did not show any reactivity, in either Western blotting or IHC. In the IHC of the gastric cancers, the expression rates of MUC4/8G7 detected by MAb 8G7, MUC4/1G8 detected by MAb 1G8 and MUC1/DF3 detected by MAb DF3 in well differentiated types (70%, 38/54; 67%, 36/54; 52%, 28/54) were significantly higher than those in poorly differentiated types (18%, 10/55; 36%, 20/55; 13%, 7/55) (

Alectinib-Induced Erythema Multiforme and Successful Rechallenge with Alectinib in a Patient with Anaplastic Lymphoma Kinase-Rearranged Lung Cancer

Background: Alectinib is an oral drug developed for the treatment of patients with fusion gene encoding echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-rearranged non-small cell lung cancer (NSCLC). Here, we present the case of a patient treated with alectinib who developed a hypersensitivity reaction with successful rechallenge treatment. Case Presentation: A 39-year-old woman who was a passive smoker was referred to Osaka City University Hospital for the evaluation of a skin event caused by treatment for NSCLC with the fusion gene EML4-ALK. The skin reaction was observed on the anterior chest, upper arms, and ear auricles on day 11 of treatment with oral alectinib. The skin event presented as widely distributed erythematous macules that were confluent, indicating a severe and life-threatening form. The skin lesions started to resolve after the initiation of treatment with 40 mg prednisolone. After regrowth of the tumor, she received a rechallenge program for alectinib for 2 weeks; thereafter, alectinib treatment was successfully reinitiated. Conclusion: To the best of our knowledge, we present the first case in which alectinib, which binds to the adenosine triphosphate site of EML4-ALK, induced erythema multiforme. Moreover, successful readministration of alectinib through our rechallenge program has not been reported so far

MUC4 and MUC1 Expression in Adenocarcinoma of the Stomach Correlates with Vessel Invasion and Lymph Node Metastasis: An Immunohistochemical Study of Early Gastric Cancer

<div><p>We have previously reported that MUC4 expression is a poor prognostic factor in various carcinomas. Our previous study also showed that MUC1 expression in gastric cancers, including the early and advanced stages is a poor prognostic factor. In the present study, the expression profiles of MUC4 and MUC1 were examined by immunohistochemistry (IHC) using two anti-MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8, and anti-MUC1 MAb DF3 in 104 gastrectomy specimens of early gastric adenocarcinoma with submucosal invasion (pT1b2), including 197 histological subtype lesions. Before the IHC study of the human specimens, we evaluated the specificity of the two MAbs by Western blotting and IHC of two MUC4 mRNA expressing gastric cancer cell lines. MAb 8G7 reacted clearly, whereas MAb 1G8 did not show any reactivity, in either Western blotting or IHC. In the IHC of the gastric cancers, the expression rates of MUC4/8G7 detected by MAb 8G7, MUC4/1G8 detected by MAb 1G8 and MUC1/DF3 detected by MAb DF3 in well differentiated types (70%, 38/54; 67%, 36/54; 52%, 28/54) were significantly higher than those in poorly differentiated types (18%, 10/55; 36%, 20/55; 13%, 7/55) (<em>P</em><0.0001; <em>P</em> = 0.0021; <em>P</em><0.0001), respectively. The MUC4/8G7 expression was related with lymphatic invasion (r = 0.304, <em>P</em> = 0.033). On the other hand, the MUC4/1G8 expression was related with lymphatic invasion (r = 0.395, <em>P</em> = 0.001) and lymph node metastasis (r = 0.296, <em>P</em> = 0.045). The MUC1/DF3 expression was related with lymphatic invasion (r = 0.357, <em>P</em> = 0.032) and venous invasion (r = 0.377, <em>P</em> = 0.024). In conclusion, the expression of MUC4 as well as MUC1 in early gastric cancers is a useful marker to predict poor prognostic factors related with vessel invasion.</p> </div

The difference in antibody specificity between anti-human MUC4 monoclonal antibodies (MAbs), 8G7 and 1G8.

<p>A: MUC4 mRNA was detected in the two gastric cancer cell lines, SNU-16 and NCI-N87. PANC1 and CAPAN1 cells were used as a negative and positive control, respectively. B: Cell lysates of SNU-16 and NCI-N87 were immunoblotted and detected by the indicated antibodies, respectively. A-tubulin served as a loading control. C: Formalin-fixed SNU-16 and NCI-N87 cells were processed for immunocytochemistry using the MAbs, 8G7 and 1G8, respectively. Original magnification ×400.</p

Clinicopathological studies using anti-MUC4 monoclonal antibodies, 8G7 and 1G8.

<p>Clinicopathological studies using anti-MUC4 monoclonal antibodies, 8G7 and 1G8.</p

Correlation among MUC4/8G7, MUC4/1G8 and MUC1/DF3.

<p>Spearman's rank-correlation coefficient.</p

Relationship between expression of MUC4 and MUC1 and lymphatic invasion (ly), venous invasion (v) or lymph node metastasis (N).

<p>Spearman's rank-correlation coefficient.</p