Fig 1.
Representative images of tumors with varying immunohistochemical scores.
Tumor cells with weak signal (intensity 1) are in the yellow circle, and tumor cells with strong signal (intensity 2) are in the red circle. In the left panels, positive signal is not detected throughout the tumor (Score 0) (A and D). In the center panels, weak signal is detected in most (90%) neoplastic cells (score 90 = 1×90) (B and E). In the right panels, strong signal is detected in most (80%) neoplastic cells (score 180 = 1×20 + 2×80) (C and F). A, B, and C are the hematoxylin and eosin stain. D, E, and F are immunohistochemistry for MUC21 with the polyclonal antibody. Magnification of all images is 200×.
Fig 2.
Correlations between MUC21 immunohistochemical scores and MUC21 mRNA levels.
MUC21 mRNA levels are displayed as a box-and-whiskers plot (median, thick line; 25th to 75th percentile, box; 10th to 90th percentile, whiskers; outliers, dots). The cut-off immunohistochemical score was set to obtain the lowest P-value for the correlation between MUC21 mRNA and each MUC21 immunohistochemical expression; MUC21P (A, cut-off value of 10), MUC21C (B, cut-off value of 70), and MUC21D (C, cut-off value of 5). Median values are described in the graphs. P values were calculated using the Mann-Whitney test. n, number of tumors examined. A total of 22 EGFR-mutated lung adenocarcinomas were examined.
Table 1.
Relationships between MUC21 expression and clinicopathological factors in lung adenocarcinomas.
Fig 3.
Representative images of three different varieties of MUC21 immunohistochemical expression.
MUC21P (A) and MUC21C (B) were expressed in lepidic elements with low papillary structure (yellow arrow) and micropapillary (mPAP) elements (blue arrowhead). MUC21D (C) was expressed only in mPAP elements (blue arrowhead). Magnification of all images is 100×.
Fig 4.
The correlations between the proportions of histological elements and the levels of MUC21 immunohistochemical expressions.
Proportions of histological elements are displayed as a box-and-whiskers plot (median, thick line; 25th to 75th percentile, box; 10th to 90th percentile, whiskers; outliers, dots). A total of 116 EGFR-mutated lung adenocarcinomas were examined. P-values were calculated using the Mann-Whitney test. High expressors of MUC21P had a significantly higher proportion of lepidic elements with low papillary structure (LEPL) and micropapillary (mPAP) elements (A). High expressors of MUC21C had a significantly greater proportion of LEPL (B). High expressors of MUC21D had a significantly greater proportion of mPAP elements (C). Abbreviations, LEPL; lepidic element with low papillary structure, ACI, acinar; PAP, papillary; mPAP, micropapillary; SOL, solid; Asterisk (*), statistically significant.
Fig 5.
Representative images of lymphatic canal invasion in a MUC21D high expressor (A, hematoxylin and eosin stain; B, immunohistochemistry for MUC21D).
A cluster of tumor cells (yellow arrowhead) strongly expressing MUC21D, which was a mixture of solid and micropapillary elements, filled a lymphatic canal. Magnification of all images is 200×.
Table 2.
Correlation between MUC21 expression and pathological factors in EGFR-mutated lung adenocarcinomas.
Fig 6.
Kaplan-Meier recurrence-free survival (RFS) curves for the association between the level of MUC21D and disease recurrence.
The RFS was significantly worse in MUC21D high expressors. A P-value was calculated using the log-rank test. n, number of tumors examined. A total of 111 patients with EGFR-mutated lung adenocarcinomas were examined with a median follow-up period of 52 months (range: 4–155 months).