Mucin Phenotype of Hyperplasia Like Lesions

Mucins are high-molecular-weight glycoproteins, with oligosaccharides attached to serine or threonine residues of the mucin core protein backbone by O-glycosidic linkages [12-14]. During the past several years, core proteins for several human mucins have been identified [12, 13, 15-18]. Among them, MUC1 and MUC2 have been examined most frequently for the studies of pancreatic intraepithelial neoplasm. Some studies showed that intraepithelial neoplasias with MUC1+/MUC2- show an aggressive nature, while those with MUC1 -/MUC2+ have an indolent nature [19, 20].

In the normal pancreas, MUC1 is expressed in the luminal surfaces of the ducts, with no intracytoplasmic or base basolateral membranous staining in the intralobular small ductules that are lined by small, cuboidal cells with minimal cytoplasm [21]. Meanwhile, no MUC2 labeling is noted in the normal pancreas [21].

Fig. 2. Two cases with hyperplastic lesion in IPMN show positive staining for MUC1 (b) and negative stain for MUC2 (c). These lesions are of flat or serrated appearance (a).

Fig. 2. Two cases with hyperplastic lesion in IPMN show positive staining for MUC1 (b) and negative stain for MUC2 (c). These lesions are of flat or serrated appearance (a).

According to our data, among 26 'hyperplasia-like lesions' from patients with IPMN, which is to be categorized as IPMN adenoma by WHO, (M:F 20:6, age 49-81, 18 branch ductile type and 8 main ductile type), MUC1 -/MUC2-(fig. 1), MUC1+/MUC2- (fig. 2) and MUC1 -/MUC2+ (fig. 3) were observed in 17, 2 and 7 cases, respectively. The degrees of atypia and accumulation of nucleus were the same among these lesions. MUC1, the membrane-bound type mucin detected in most epithelial tissues, was stained at the apical site of the epithelium, while MUC2, an intestinal-type mucin, was diffusely stained in the epithelium. MUC1+/ MUC2- lesions showed a serrated appearance without a papillary intestinal core, while MUC1-/MUC2+ lesions consisted of papillas with an intestinal core. The averages of their height were 0.34 ± 0.21 mm (0.1-0.8 mm), 0.14 ± 0.01mm (0.13-0.15mm) and 0.66 ± 0.54 mm (0.15-1.5mm) in each lesion of MUC1 -/MUC2-, MUC1+/MUC2- and MUC1 -/MUC2+, respectively (Kruskal-Wallis test, p = 0.13). MUC1+/MUC2- lesions tend to be lower papilla, while MUC1 -/MUC2+ lesions tend to be higher, albeit not statistically significant. We also examined the MUC1/MUC2 expression pattern among 12 PanIN-1 lesions from 6 patients with invasive pancreatic cancer (M:F

Fig. 3. Seven cases with hyperplastic lesion in IPMN show negative staining for MUC1 (b) and positive stain for MUC2 (c). These lesions show papilla with intestinal core (a).

2:4, age 56-68). Seven of them showed MUC1-/MUC2-, and 5 lesions showed MUC1+/MUD2- (fig. 4). None of them showed MUC1-/MUC2+.

Our data suggested the possible overlap of lesions, both between low-grade neoplasia and hyperplasia, and between IPMN and PanIN, as follows:

MUC1-/MUC2- intraepithelial lesions, showing the same pattern observed among normal pancreatic ducts, might fall into the category of non-neoplastic lesions, in spite of their indistinguishable morphological features.

IPMN adenoma with MUC1+/MUC2- might be close to PanIN-1 with MUC1+/MUC2-, having both the same MUC1/MUC2 pattern and low-height morphology.

Fig. 4. Some PanIN-1 lesions (a) show partly positive staining for MUC1 (b, arrow), and totally negative stain for MUC2 (c).

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