探讨Toll样受体2(TLR2)和Toll样受体4(TLR4)在不同病理类型及不同临床分期非哺乳期乳腺炎(NPM)中的表达及其意义。

本研究为回顾性研究。选取2012年1月至2017年1月在南京医科大学附属淮安第一医院行手术治疗的141例NPM患者及10例乳腺纤维瘤患者(对照组)的病理切片进行TLR2、TLR4表达水平的免疫组织化学检测。根据术后病理结果将NPM分为肉芽肿性乳腺炎(GM)59例，浆细胞性乳腺炎(PCM)50例，其他类型乳腺炎32例，并将其中GM、PCM与对照组进行对比研究。根据临床分期将141例患者分为急性期(21例)、亚急性期(72例)、慢性期(48例)，并与对照组进行对比研究。通过检测TLR2、TLR4在不同病理类型及不同临床分期NPM中的表达水平，同时结合临床资料进行统计分析。多组间TLR2、TLR4表达水平的比较采用单因素方差分析，方差整齐时两两比较采用LSD法，方差不齐时两两比较采用Tamhane’s法；GM与PCM患者临床特征的比较采用χ²检验。

GM组TLR2、TLR4表达水平分别为15.82±4.96和27.27±7.70，PCM组TLR2、TLR4表达水平分别为15.29±4.14和26.25±6.63，对照组TLR2、TLR4表达水平分别为6.12±0.81和6.40±1.18。3组相比，TLR2、TLR4表达水平的差异均有统计学意义(F＝21.613、39.746，P均<0.001)，其中GM、PCM组TLR2、TLR4表达水平均高于对照组(P均<0.050)。并且，急性期、亚急性期、慢性期NPM及对照组患者相比，TLR2、TLR4表达水平的差异均有统计学意义(F＝190.112、246.965，P均<0.001)，其中急性期NPM患者TLR2、TLR4表达水平分别为23.65±2.32和40.10±2.22，高于亚急性期NPM的12.35±2.44和23.14±4.56(P均<0.001)，也高于慢性期NPM的17.19±2.36和29.36±2.17(P均<0.001)。与PCM患者相比，GM患者下肢结节红斑的发生率较高[28.8%(17/59)比12.0%(6/50)，χ²＝4.596，P＝0.032]。

TLR2和TLR4在急性期NPM中显著高表达，TLR2、TLR4信号途径可能参与NPM的发生、发展；GM与PCM患者的下肢结节红斑发生率存在差异。

To explore the expression and clinical significance of Toll-like receptor (TLR) 2 and TLR4 in non-puerperal mastitis (NPM) of different pathological types and clinical stages.

This was a retrospective analysis. The pathological sections from 141 patients with NPM and 10 patients with breast fibroma (control group) who underwent surgical treatment in the First Affiliated Huai’an Hospital of Nanjing Medical University from January 2012 to January 2017 were immunohistochemically detected. According to the postoperative pathological results, NPM patients was divided into granulomatous mastitis (GM, n=59), plasma cell mastitis (PCM, n=50) and other types of mastitis(n=32), and then the patients with GM or PCM were compared with patients with breast fibroma (control group). According to the clinical stage, 141 NPM patients were divided into acute stage (n=21), subacute stage (n=72) and chronic stage (n=48), which was compared with the control group, respectively. The expression levels of TLR2 and TLR4 in NPM of different pathological types and different clinical stages were determined, and then statistical analysis was carried out in combination with clinical data. The one-way analysis of variance was used to compare the expression levels of TLR2 and TLR4 among multiple groups. With heterogeneity of variance, the Tamhane’s method was used for pairwise comparison, otherwise, the LSD method was used for pairwise comparison. The clinical characteristics were compared between GM and PCM patients by χ² test.

The expression levels of TLR2 and TLR4 were 15.82 ± 4.96 and 27.27 ± 7.70 in the GM group, 15.29 ± 4.14 and 26.25 ± 6.63 in the PCM group, 6.12 ± 0.81 and 6.40 ±1.18 in the control group, respectively, indicating a significant difference among three groups (F= 21.613, 39.746, both P<0.001). The expression levels of TLR2 and TLR4 in the GM and PCM groups were significantly higher than those in the control group (all P<0.050). Moreover, the expression levels of TLR2 and TLR4 in NPM patients presented a significant difference among the acute phase, subacute phase, chronic phase groups and the control group (F=190.112, 246.965, both P<0.001). The expression levels of TLR2 and TLR4 in patients with acute NPM were 23.65 ± 2.32 and 40.10 ± 2.22, which were significantly higher than those in subacute NPM (12.35 ± 2.44 and 23.14 ± 4.56, both P<0.001), and those in chronic NPM (17.19± 2.36 and 29.36 ± 2.17, both P<0.001). GM patients had a significantly higher incidence of erythema nodosa in lower extremities compared with PCM patients [28.8% (17/59) vs 12.0% (6/50), χ² = 4.596, P=0.032].

TLR2 and TLR4 are highly expressed in acute NPM, and the TLR2/TLR4 signaling pathway may be involved in the occurrence and development of NPM. There is a significant difference in the incidence of erythema nodosa in lower extremities between GM and PCM patients.