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. 2014 Oct 22;5(9):754-60.
doi: 10.7150/jca.10238. eCollection 2014.

Perineural Invasion and TAMs in Pancreatic Ductal Adenocarcinomas: Review of the Original Pathology Reports Using Immunohistochemical Enhancement and Relationships with Clinicopathological Features

Linjuan Zeng  1 , Yubo Guo  2 , Jianzhong Liang  3 , Shaojie Chen  2 , Peijian Peng  4 , Qiubo Zhang  5 , Hong Su  2 , Yinting Chen  2 , Kaihong Huang  2
Affiliations

Perineural Invasion and TAMs in Pancreatic Ductal Adenocarcinomas: Review of the Original Pathology Reports Using Immunohistochemical Enhancement and Relationships with Clinicopathological Features

Linjuan Zeng et al. J Cancer. .

Abstract

Objectives: Tumor-associated macrophages (TAMs) are thought to be involved in the perineural invasion (PNI) process and to be associated with poor prognoses. The associations between TAMs, PNI, and clinicopathological features in pancreatic ductal adenocarcinomas (PDAs) remain to be elucidated.

Methods: Fifty-nine PDA patients who had undergone pancreaticoduodenectomy were retrospectively examined. The PNI statuses and TAMs were reviewed following H&E staining and S-100, CD68, and CD163 immunohistochemical staining. The relationships between PNI, TAMs, and overall survival and various clinical and histopathologic factors were investigated.

Results: PNI was identified in 83% (49/59) of the cases, the TAM density of the PNI(+) group was greater than that of the PNI(-) group, and the infiltrating TAMs around the nerves that were invaded by cancer were much more numerous than those around the nerves without cancer cell invasion. The incidences of PNI, lymph node metastasis, high serum CA19-9 level, cancers in the body/tail, and advanced pathological stage were associated with shorter OSs. In the PNI(+) group, lymph node metastasis and high levels of TAM infiltration were associated with worse prognoses.

Conclusions: TAMs might enhance PNI, and the incidence of PNI was associated with poor prognosis. PNI(+) status and high levels of TAM infiltration further worsen the prognosis. Therapies targeting TAMs might represent auxiliary and preventive treatment for PNI in PDA patients.

Keywords: immunohistochemical; lymph node metastasis.; pancreatic ductal adenocarcinomas; perineural invasion; tumor associated macrophages.

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Conflict of interest statement

Competing Interests: There is no financial interest to report that might pose a potential, perceived or real conflict of interest.

Figures

Figure 1
Figure 1
Representative images of nerves with H&E and S-100 immunolabeling staining. The macrophages were studied using immunolabeling with the macrophage marker CD68 and the M2-type macrophage marker CD163. (A), (E) H&E staining of the nerves. (B), (F) S-100 immunohistochemical staining of the nerves. (C), (G) CD68 immunohistochemical staining of the macrophages. (D), (H) CD163 immunohistochemical staining of the macrophages. (A) to (D), Tumor tissue samples with intra-PDA lesions. (E) to (H), Benign pancreatic tissues. (a) to (h) Magnified images of (A) to (H), respectively. PDA, pancreatic ductal adenocarcinoma. N, nerve's bundle. Positive staining is shown in brown.
Figure 2
Figure 2
The macrophage counts around nerves with and without cancer cell infiltration. PDA cell (+), nerves infiltrated by PDAs cells; PDA cell (-), nerves not included in a cancer foci without direct contact between them. The data are shown as the means ± the S.Es (n = 49). * P < 0.05 compared to PDA cell (-), Ɨ P < 0.05 compared to benign pancreatic tissues. Abbreviations: PDA, pancreatic ductal adenocarcinoma.
Figure 3
Figure 3
(A) Overall survival curves (OS) for the PDA patients according to the PNI incidence. The OS periods were significantly shorter for the patients with PNI than for the patients without PNI. Among the PNI+ patients, lymph node metastasis (B), CD68 high (C) and CD163 high (D) were associated with poorer prognoses. Abbreviations: PNI, peripheral neural invasion. LN, lymph node metastasis.
See this image and copyright information in PMC

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