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

Zeng L, Guo Y, Liang J, Chen S, Peng P, Zhang Q, Su H, Chen Y, Huang K - J Cancer (2014)

Bottom Line: 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.PNI(+) status and high levels of TAM infiltration further worsen the prognosis.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University. The 52th of Meihua East Road, Zhuhai 519000, China ; 2. Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University. The 107th of Yanjiang West Road, GuangZhou 510120, China.

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.

No MeSH data available.


Related in: MedlinePlus

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.
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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.

Mentions: Macrophages are one of the most common inflammatory cell types involved in the host stromal response to cancer cell invasion 16. To explore the macrophage response to PNI, we evaluated the TAM densities and patterns of macrophage infiltration around the nerves in pathological specimens excised from 59 patients with PDAs. As shown in Figure 1, the macrophages were studied with immunolabeling for the macrophage marker CD68, the M2-type macrophages marker CD163, and S-100 staining of the nerves. Table 1shows the relationship between the macrophages and PNI. The numbers of CD68+and CD163+ cells within the PDA lesions in the PNI+ group were higher than those of the PNI- group (105 ± 3.77 vs. 86 ± 9.57 for the CD68+ cells, P = 0.04; and 73 ± 4.83 vs. 46 ± 8.04 for the CD163+ cells, P = 0.017, respectively.). Although there was no significant relationship between the macrophage counts and PNI grades, infiltrating CD68+and CD163+ cells were much more commonly found around the nerves that had been invaded by cancer than around those that had not (7.92 ± 0.81 vs. 4.47 ± 0.55 CD68+ macrophages/nerve, P = 0.000, and 4.98 ± 0.62 vs. 3.03 ± 0.57 CD163+ macrophages/nerve, P = 0.001, respectively). Notably, the nerves in the PDAs lesion that had not been invaded by cancer cells were surrounded by greater numbers of CD68+and CD163+ cells than were the nerves in the benign areas of pancreatic tissues (4.47 ± 0.55 vs. 2.00 ± 0.71 CD68+ macrophages/nerve, P = 0.000, and 3.03 ± 0.57 vs. 0.23 ± 0.17 CD163+ macrophages/nerve, P = 0.018, respectively, Figure 2), which indicates that the TAMs enhanced cancer cell invasion along the nerves.


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

Zeng L, Guo Y, Liang J, Chen S, Peng P, Zhang Q, Su H, Chen Y, Huang K - J Cancer (2014)

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.
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Related In: Results  -  Collection

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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.
Mentions: Macrophages are one of the most common inflammatory cell types involved in the host stromal response to cancer cell invasion 16. To explore the macrophage response to PNI, we evaluated the TAM densities and patterns of macrophage infiltration around the nerves in pathological specimens excised from 59 patients with PDAs. As shown in Figure 1, the macrophages were studied with immunolabeling for the macrophage marker CD68, the M2-type macrophages marker CD163, and S-100 staining of the nerves. Table 1shows the relationship between the macrophages and PNI. The numbers of CD68+and CD163+ cells within the PDA lesions in the PNI+ group were higher than those of the PNI- group (105 ± 3.77 vs. 86 ± 9.57 for the CD68+ cells, P = 0.04; and 73 ± 4.83 vs. 46 ± 8.04 for the CD163+ cells, P = 0.017, respectively.). Although there was no significant relationship between the macrophage counts and PNI grades, infiltrating CD68+and CD163+ cells were much more commonly found around the nerves that had been invaded by cancer than around those that had not (7.92 ± 0.81 vs. 4.47 ± 0.55 CD68+ macrophages/nerve, P = 0.000, and 4.98 ± 0.62 vs. 3.03 ± 0.57 CD163+ macrophages/nerve, P = 0.001, respectively). Notably, the nerves in the PDAs lesion that had not been invaded by cancer cells were surrounded by greater numbers of CD68+and CD163+ cells than were the nerves in the benign areas of pancreatic tissues (4.47 ± 0.55 vs. 2.00 ± 0.71 CD68+ macrophages/nerve, P = 0.000, and 3.03 ± 0.57 vs. 0.23 ± 0.17 CD163+ macrophages/nerve, P = 0.018, respectively, Figure 2), which indicates that the TAMs enhanced cancer cell invasion along the nerves.

Bottom Line: 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.PNI(+) status and high levels of TAM infiltration further worsen the prognosis.

View Article: PubMed Central - PubMed

Affiliation: 1. Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University. The 52th of Meihua East Road, Zhuhai 519000, China ; 2. Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University. The 107th of Yanjiang West Road, GuangZhou 510120, China.

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.

No MeSH data available.


Related in: MedlinePlus