| Objective: The clinicopathological data of mammary Paget’s disease(MPD)and extramammary disease(EMPD)were reviewed retrospectively.Study on the expression,correlation and clinical significance of proteins such as AK4,NR5A2,LPP were conducted.We aim to further investigate the histochemical markers of MPD and EMPD to illustrate the biological significance of these markers in MPD and EMPD.Methods: 1.The clinical and pathological data of MPD and EMPD patients treated in the First Affiliated Hospital of China Medical University in recent 5 years were retrospectively analyzed.2.Twenty-one samples of MPD and 19 of EMPD were selected,and an MPD tissue microarray and an EMPD tissue microarray were made,respectively.The expressions of AK4,NR5A2,LPP proteins were studied by immunohistochemistry and the dyeing strength was judged according to Campo standard.The number of Paget cells(PCs)per unit area,the length of epidermal rete ridge,the thickness of spinous layer,the depth of inflammatory cell infiltration,disruption of spinous layer and adnexal metastasis were counted by Case Viewer.The clinical significance was analyzed by combining the clinical data and other immunohistochemical results(including ER,PR,Ki-67 and C-erb B-2).3.Analysis was performed using IBM SPSS Statistics 25(SPSS Inc.,Chicago,IL,U.S.A.)and Graph Pad Prism 8.0,and x~2-tests,independent sample t test,one-way analysis of variance,rank sum test was used to evaluate the relationship between the immunostaining and clinicopathological parameters.P < 0.05 was considered to indicate statistical significance.Results:1.Clinical data:(1)MPD:There were 21 female patients with an average age of onset of 61.0years and a median age of onset of 63.0 years.All of the the lesions were unilateral in distribution.52.3%(11 / 21)of the lesiosn were on the left side,47.7%(10 / 21)on the right side,71.4%(15 / 21)with ulceration,21.6%(6 /21)with no ulceration,66.7%(14 / 21)with nipple discharge and 33.3%(7 /21)with no nipple discharge.Among the 21 samples,18 samples had been tested for ER expression,including 6 samples with ER(+)and 12 samples with ER(-).Sixteen samples had been tested for PR expression,including 5samples with PR(+),11 samples with PR(-).Seventeen samples were tested for Ki-67 expression,all of which were positive,of which 4 samples had less than 15% positive cells,13 samples had more than 15% positive cells.And 15 samples had been tested for c-erb B-2 expression,which were all positive,including 6 samples graded 2(+)and 9 samples graded 3(+).(2)EMPD: There were 19 cases,including 13 males and 6 females.The mean age of onset was 63.2 years old.The median age of onset was 61.5 years old.26.4%(5 / 19)of the patients were from vulva,52.6%(10 / 19)of them were from scrotum,10.5%(2 / 19)of them were from penis,and 10.5%(2 / 19)were from axilla.2.Histopathology(1)MPD and EMPD were similar in histopathology which showed epidermal hyperplasia and Paget cells which had atypical round or oval nuclei and rich basophil,hermaphroditic or transparent cytoplasm can be seen throughout the epidermis.PCs are in the form of single cells or clusters.(2)The average thickness of spinous layer in MPD was 219 um,and that in EMPD was 316um(P=0.043).There was no significant difference in the number of PCs per unit epidermis area(P=0.211),the length of epidermal rete ridge(P=0.091)and the infiltration depth of inflammatory cells in dermis between MPD and EMPD(P=0.715).3.Immunohistochemistry(1)AK4 was expressed in the cytoplasm of 21 cases of MPD and 19 cases of EMPD.AK4 expression in MPD was higher than that of EMPD.In MPD,the number of strong positive,medium positive and weak positive samples were 7,9 and 5,respectively.In EMPD,they are 1,4,14,respectively.The difference is statistically significant(P=0.02).(2)NR5A2 was weakly expressed in the nuclei of 21 cases of MPD and 19 cases of EMPD.There was no significant difference between them.(3)LPP was expressed in the cytoplasm of 21 cases of MPD and 19 cases of EMPD.LPP expression in MPD was higher than that of EMPD.In MPD,the number of strong positive,medium positive and weak positive samples were 8,6 and 7,respectively.In EMPD,they are 1,7,11,respectively.The difference is statistically significant(P=0.031).(4)In MPD,the expression of AK4 in the lesions with ulceration group was stronger than that without ulceration group(P=0.045),ER(-)group was stronger than ER(+)group(P=0.039).(5)In MPD,the expression of LPP in middle-aged group was higher than that in the senior group(P=0.009),and Ki-67 > 15% group was higher than Ki-67 <15% group(P=0.011).Conclusion : 1.MPD and EMPD are difficult to distinguish under conventional pathology examination.2.There was no difference in the number of PCs per unit area,the depth of inflammatory cell infiltration and the average length of epidermal process between EMPD and MPD.3.AK4 and LPP were both positive in MPD and EMPD,but the expression intensity of MPD was higher than that of EMPD;NR5A2 was weakly positive in both MPD and EMPD,and there was no difference between them.4.In MPD,the expression of AK4 in the lesions with ulceration and ER(-)groups was higher than that in the lesions without ulceration and ER(+)groups.It is speculated that the expression of AK4 can be used as a prognostic indicator of MPD.5.In MPD,the expression of LPP in middle-aged group and Ki-67 > 15% group was stronger than that in senior group and Ki-67 < 15% group.It is speculated that LPP is related to the occurrence and spread of MPD,and more studies are needed to confirm. |
