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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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The classification of PNI in different group.Ne0–no perineural invasion; Ne1–neurium invasion; Ne2–perineural space invasion; Ne3–nerve bundle invasion. The nerve structures (A, B) and representative stages of the invaded neural structure for classification (C–H). (A) A nerve bundle surrounded by the continuous layered epithelioid sheets of the perineurium (arrowhead). (B) The perineural space, an internal space between the nerve bundle and perineurium (arrowhead). (C) Neurium invasion of cancer cells in the outer perineural space and attached to the perineurium (arrowhead). (D) Perineurial cells of perineurium between the nerve bundle and cancer cells (arrowhead). (E) Perineural space invasion of cancer cells in the perineural space (arrowhead). (F) Cancer cells invading the perineural space and compressing the nerve bundle smoothly. The border between cancer cells and nerve bundles do not contain perineurial cells or perineurium (arrowhead). (G) Nerve bundle invasion by cancer cells. Cancer cells irregularly compress the nerve bundle, clearly invading between nerve fibers (arrowhead). (H) Invasive cancer cells clearly seen between nerve fibers (arrowhead). A, C, E, G show an original magnification of 100×, and B, D, F, H an original magnification of 400×. Figure arrowheads indicate the nerves.
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pone-0017385-g005: The classification of PNI in different group.Ne0–no perineural invasion; Ne1–neurium invasion; Ne2–perineural space invasion; Ne3–nerve bundle invasion. The nerve structures (A, B) and representative stages of the invaded neural structure for classification (C–H). (A) A nerve bundle surrounded by the continuous layered epithelioid sheets of the perineurium (arrowhead). (B) The perineural space, an internal space between the nerve bundle and perineurium (arrowhead). (C) Neurium invasion of cancer cells in the outer perineural space and attached to the perineurium (arrowhead). (D) Perineurial cells of perineurium between the nerve bundle and cancer cells (arrowhead). (E) Perineural space invasion of cancer cells in the perineural space (arrowhead). (F) Cancer cells invading the perineural space and compressing the nerve bundle smoothly. The border between cancer cells and nerve bundles do not contain perineurial cells or perineurium (arrowhead). (G) Nerve bundle invasion by cancer cells. Cancer cells irregularly compress the nerve bundle, clearly invading between nerve fibers (arrowhead). (H) Invasive cancer cells clearly seen between nerve fibers (arrowhead). A, C, E, G show an original magnification of 100×, and B, D, F, H an original magnification of 400×. Figure arrowheads indicate the nerves.

Mentions: Representative images of normal structures of the nerves and the invading neural structure in various stages of classification in pancreatic tissues are shown in Fig. 5. A nerve bundle surrounded by the continuously layered epithelioid sheets is called the perineurium, while the internal space between the nerve bundle and perineurium is the perineural space. The degree of PNI was classified into four grades according to the presence of cancer cells in the different structures of the nerve tissues. As shown in Table 3, the total frequency of PNI was higher in the hyperglycemia group than that in the euglycemia group with no statistically significant difference. However, the frequency of the Ne3 invasion was significantly higher in the hyperglycemia group than that in the euglycemia group (p = 0.000, continuity correction).


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)

The classification of PNI in different group.Ne0–no perineural invasion; Ne1–neurium invasion; Ne2–perineural space invasion; Ne3–nerve bundle invasion. The nerve structures (A, B) and representative stages of the invaded neural structure for classification (C–H). (A) A nerve bundle surrounded by the continuous layered epithelioid sheets of the perineurium (arrowhead). (B) The perineural space, an internal space between the nerve bundle and perineurium (arrowhead). (C) Neurium invasion of cancer cells in the outer perineural space and attached to the perineurium (arrowhead). (D) Perineurial cells of perineurium between the nerve bundle and cancer cells (arrowhead). (E) Perineural space invasion of cancer cells in the perineural space (arrowhead). (F) Cancer cells invading the perineural space and compressing the nerve bundle smoothly. The border between cancer cells and nerve bundles do not contain perineurial cells or perineurium (arrowhead). (G) Nerve bundle invasion by cancer cells. Cancer cells irregularly compress the nerve bundle, clearly invading between nerve fibers (arrowhead). (H) Invasive cancer cells clearly seen between nerve fibers (arrowhead). A, C, E, G show an original magnification of 100×, and B, D, F, H an original magnification of 400×. Figure arrowheads indicate the nerves.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3046240&req=5

pone-0017385-g005: The classification of PNI in different group.Ne0–no perineural invasion; Ne1–neurium invasion; Ne2–perineural space invasion; Ne3–nerve bundle invasion. The nerve structures (A, B) and representative stages of the invaded neural structure for classification (C–H). (A) A nerve bundle surrounded by the continuous layered epithelioid sheets of the perineurium (arrowhead). (B) The perineural space, an internal space between the nerve bundle and perineurium (arrowhead). (C) Neurium invasion of cancer cells in the outer perineural space and attached to the perineurium (arrowhead). (D) Perineurial cells of perineurium between the nerve bundle and cancer cells (arrowhead). (E) Perineural space invasion of cancer cells in the perineural space (arrowhead). (F) Cancer cells invading the perineural space and compressing the nerve bundle smoothly. The border between cancer cells and nerve bundles do not contain perineurial cells or perineurium (arrowhead). (G) Nerve bundle invasion by cancer cells. Cancer cells irregularly compress the nerve bundle, clearly invading between nerve fibers (arrowhead). (H) Invasive cancer cells clearly seen between nerve fibers (arrowhead). A, C, E, G show an original magnification of 100×, and B, D, F, H an original magnification of 400×. Figure arrowheads indicate the nerves.
Mentions: Representative images of normal structures of the nerves and the invading neural structure in various stages of classification in pancreatic tissues are shown in Fig. 5. A nerve bundle surrounded by the continuously layered epithelioid sheets is called the perineurium, while the internal space between the nerve bundle and perineurium is the perineural space. The degree of PNI was classified into four grades according to the presence of cancer cells in the different structures of the nerve tissues. As shown in Table 3, the total frequency of PNI was higher in the hyperglycemia group than that in the euglycemia group with no statistically significant difference. However, the frequency of the Ne3 invasion was significantly higher in the hyperglycemia group than that in the euglycemia group (p = 0.000, continuity correction).

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