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Relationship between neural alteration and perineural invasion in pancreatic cancer patients with hyperglycemia.

Li J, Ma Q, Liu H, Guo K, Li F, Li W, Han L, Wang F, Wu E - PLoS ONE (2011)

Bottom Line: The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm(2) were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively).The integrated optical density (IOD) of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019), while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively).The abnormal expression of NGF and p75 may also be involved in this process and subsequently lead to a lower rate of curative surgery.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

ABSTRACT

Background: Patients with higher levels of fasting serum glucose have higher death rates from pancreatic cancer compared to patients with lower levels of fasting serum glucose. However, the reasons have not been studied. The goal of the current study was to examine the neural alterations in pancreatic cancer patients with hyperglycemia and to identify the relationship between the neural alterations and perineural invasion.

Methodology/principal findings: The clinical and pathological features of 61 formalin-fixed pancreatic cancer specimens and 10 normal pancreases as controls were analyzed. Furthermore, the expression of Protein Gene Product 9.5 (PGP9.5), Myelin P0 protein (MPP), NGF, TrkA, and p75 were examined by immunohistochemistry. The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm(2) were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively). The integrated optical density (IOD) of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019), while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively). The nerve bundle invasion of pancreatic cancer was more frequent in the hyperglycemia group than in the euglycemia group (p = 0.000).

Conclusions/significance: Nerve damage and regeneration occur simultaneously in the tumor microenvironment of pancreatic cancer patients with hyperglycemia; the simultaneous occurrence may aggravate the process of perineural invasion. The abnormal expression of NGF and p75 may also be involved in this process and subsequently lead to a lower rate of curative surgery.

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NGF, TrkA, and p75 immunostaining of pancreatic cancer tissue in the euglycemia group and hyperglycemia group.A, C, E, G, I, K show an original magnification of 100×, and B, D, F, H, J, L an original magnification of 400×. The frequency of moderate to strong NGF staining of cancer cells was significantly higher in the hyperglycemia group than that in the euglycemia group (arrowhead). The NGF stain of nerves was not significantly different between the two groups. The moderate to strong TrkA stainings were also present in the two groups (arrowhead) but with no significant difference. The frequency of moderate to strong p75 staining of nerves (arrowhead) was significantly higher in the hyperglycemia group than that in the euglycemia group. Figure arrowheads indicate the immunostainings.
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pone-0017385-g003: NGF, TrkA, and p75 immunostaining of pancreatic cancer tissue in the euglycemia group and hyperglycemia group.A, C, E, G, I, K show an original magnification of 100×, and B, D, F, H, J, L an original magnification of 400×. The frequency of moderate to strong NGF staining of cancer cells was significantly higher in the hyperglycemia group than that in the euglycemia group (arrowhead). The NGF stain of nerves was not significantly different between the two groups. The moderate to strong TrkA stainings were also present in the two groups (arrowhead) but with no significant difference. The frequency of moderate to strong p75 staining of nerves (arrowhead) was significantly higher in the hyperglycemia group than that in the euglycemia group. Figure arrowheads indicate the immunostainings.

Mentions: The majority of cancer cells and nerve tissues showed distinct immunostainings of TrkA, P75NTR, and NGF localized to the cytoplasm. The nerve tissues had different expression levels of TrkA and p75NTR by immunostaining between the euglycemia group and hyperglycemia group. (Fig. 3). As shown in Fig. 4, the NGF staining in the cytoplasm of the cancer cells was significantly stronger (p = 0.002) in the hyperglycemia group than in the euglycemia group, indicating the NGF protein level of cancer cells was increased in the hyperglycemia group. The percentage of cancer area occupied by positive NGF staining cancer cells was significantly higher in the hyperglycemia group than in the euglycemia group. In the cross section of the nerves, the TrkA immunostaining of nerve fibers was equivalent in the two groups with no significant differences (p = 0.626). The p75NTR immunostaining had a peripheral pattern, where the surrounding area of nerve fibers was strongly stained and the central area was mildly stained in the hyperglycemia group; in contrast, the p75NTR immunostaining in the euglycemia group was light and uniform (p = 0.026).


Relationship between neural alteration and perineural invasion in pancreatic cancer patients with hyperglycemia.

Li J, Ma Q, Liu H, Guo K, Li F, Li W, Han L, Wang F, Wu E - PLoS ONE (2011)

NGF, TrkA, and p75 immunostaining of pancreatic cancer tissue in the euglycemia group and hyperglycemia group.A, C, E, G, I, K show an original magnification of 100×, and B, D, F, H, J, L an original magnification of 400×. The frequency of moderate to strong NGF staining of cancer cells was significantly higher in the hyperglycemia group than that in the euglycemia group (arrowhead). The NGF stain of nerves was not significantly different between the two groups. The moderate to strong TrkA stainings were also present in the two groups (arrowhead) but with no significant difference. The frequency of moderate to strong p75 staining of nerves (arrowhead) was significantly higher in the hyperglycemia group than that in the euglycemia group. Figure arrowheads indicate the immunostainings.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3046240&req=5

pone-0017385-g003: NGF, TrkA, and p75 immunostaining of pancreatic cancer tissue in the euglycemia group and hyperglycemia group.A, C, E, G, I, K show an original magnification of 100×, and B, D, F, H, J, L an original magnification of 400×. The frequency of moderate to strong NGF staining of cancer cells was significantly higher in the hyperglycemia group than that in the euglycemia group (arrowhead). The NGF stain of nerves was not significantly different between the two groups. The moderate to strong TrkA stainings were also present in the two groups (arrowhead) but with no significant difference. The frequency of moderate to strong p75 staining of nerves (arrowhead) was significantly higher in the hyperglycemia group than that in the euglycemia group. Figure arrowheads indicate the immunostainings.
Mentions: The majority of cancer cells and nerve tissues showed distinct immunostainings of TrkA, P75NTR, and NGF localized to the cytoplasm. The nerve tissues had different expression levels of TrkA and p75NTR by immunostaining between the euglycemia group and hyperglycemia group. (Fig. 3). As shown in Fig. 4, the NGF staining in the cytoplasm of the cancer cells was significantly stronger (p = 0.002) in the hyperglycemia group than in the euglycemia group, indicating the NGF protein level of cancer cells was increased in the hyperglycemia group. The percentage of cancer area occupied by positive NGF staining cancer cells was significantly higher in the hyperglycemia group than in the euglycemia group. In the cross section of the nerves, the TrkA immunostaining of nerve fibers was equivalent in the two groups with no significant differences (p = 0.626). The p75NTR immunostaining had a peripheral pattern, where the surrounding area of nerve fibers was strongly stained and the central area was mildly stained in the hyperglycemia group; in contrast, the p75NTR immunostaining in the euglycemia group was light and uniform (p = 0.026).

Bottom Line: The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm(2) were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively).The integrated optical density (IOD) of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019), while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively).The abnormal expression of NGF and p75 may also be involved in this process and subsequently lead to a lower rate of curative surgery.

View Article: PubMed Central - PubMed

Affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

ABSTRACT

Background: Patients with higher levels of fasting serum glucose have higher death rates from pancreatic cancer compared to patients with lower levels of fasting serum glucose. However, the reasons have not been studied. The goal of the current study was to examine the neural alterations in pancreatic cancer patients with hyperglycemia and to identify the relationship between the neural alterations and perineural invasion.

Methodology/principal findings: The clinical and pathological features of 61 formalin-fixed pancreatic cancer specimens and 10 normal pancreases as controls were analyzed. Furthermore, the expression of Protein Gene Product 9.5 (PGP9.5), Myelin P0 protein (MPP), NGF, TrkA, and p75 were examined by immunohistochemistry. The median number of nerves, the median area of neural tissue, and the median nerve diameter per 10 mm(2) were larger in the hyperglycemia group than those in the euglycemia group (p = 0.007, p = 0.009, and p = 0.004, respectively). The integrated optical density (IOD) of MPP staining was lower in the hyperglycemia group than those in the euglycemia group (p = 0.019), while the expression levels of NGF and p75 were higher in the hyperglycemia group than those in the euglycemia group (p = 0.002, and p = 0.026, respectively). The nerve bundle invasion of pancreatic cancer was more frequent in the hyperglycemia group than in the euglycemia group (p = 0.000).

Conclusions/significance: Nerve damage and regeneration occur simultaneously in the tumor microenvironment of pancreatic cancer patients with hyperglycemia; the simultaneous occurrence may aggravate the process of perineural invasion. The abnormal expression of NGF and p75 may also be involved in this process and subsequently lead to a lower rate of curative surgery.

Show MeSH
Related in: MedlinePlus