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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

(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.
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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.

Mentions: There were no significant correlations of PNI with pathological stage, pathological grade, or lymph node metastasis in the PDAs (data not shown). The relationships between various clinicopathological features and PNI in the PDAs are shown in Table 2. The incidence of PNI was significantly correlated with abdominal pain (P = 0.000), and the levels of Glu in the patients with PNI were significantly higher than those in the patients without PNI (8.77 ± 3.80 vs. 6.25 ± 1.03, P = 0.043). There were no significant relationships of PNI with serum LDH, CRP, or CA199 levels. The results of univariate analyses of the associations of the prognostic factors with OS are shown in Table 3. The incidences of PNI, lymph node metastasis, high serum CA19-9 level, cancers in the body and tail, and advanced pathological stage were associated with poor prognosis. The mean OS of the PNI- group was significantly longer than that of the PNI+ group (21.20 ± 3.36 vs. 13.12 ± 1.08, P = 0.006), but there were no significant differences among the PNI+ sub-groups. The mean OSs of the ne1, ne2 and ne3 sub-groups were 14.33 (± 1.41), 10.64 (± 1.65), and 11.38 (± 3.14), respectively (P > 0.05). Our results indicate that the incidence but not the severity of PNI affected the prognoses of PDAs. The OS curves (Kaplan-Meier) plotted according to PNI incidence, lymph node metastasis and macrophage counts are shown in Figure 3. Among the patients with PNI, lymph node involvement was associated with worse prognosis (P = 0.002), and the CD68high and CD163high patients had worse prognoses than did the CD68low (P = 0.028) and CD163low (P = 0.004) patients.


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)

(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.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4216799&req=5

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.
Mentions: There were no significant correlations of PNI with pathological stage, pathological grade, or lymph node metastasis in the PDAs (data not shown). The relationships between various clinicopathological features and PNI in the PDAs are shown in Table 2. The incidence of PNI was significantly correlated with abdominal pain (P = 0.000), and the levels of Glu in the patients with PNI were significantly higher than those in the patients without PNI (8.77 ± 3.80 vs. 6.25 ± 1.03, P = 0.043). There were no significant relationships of PNI with serum LDH, CRP, or CA199 levels. The results of univariate analyses of the associations of the prognostic factors with OS are shown in Table 3. The incidences of PNI, lymph node metastasis, high serum CA19-9 level, cancers in the body and tail, and advanced pathological stage were associated with poor prognosis. The mean OS of the PNI- group was significantly longer than that of the PNI+ group (21.20 ± 3.36 vs. 13.12 ± 1.08, P = 0.006), but there were no significant differences among the PNI+ sub-groups. The mean OSs of the ne1, ne2 and ne3 sub-groups were 14.33 (± 1.41), 10.64 (± 1.65), and 11.38 (± 3.14), respectively (P > 0.05). Our results indicate that the incidence but not the severity of PNI affected the prognoses of PDAs. The OS curves (Kaplan-Meier) plotted according to PNI incidence, lymph node metastasis and macrophage counts are shown in Figure 3. Among the patients with PNI, lymph node involvement was associated with worse prognosis (P = 0.002), and the CD68high and CD163high patients had worse prognoses than did the CD68low (P = 0.028) and CD163low (P = 0.004) patients.

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