It is now clear that the association between cancer cells and recruited fibroblasts (cancer-associated fibroblasts; CAFs) leads to alteration of the biological properties of both types of cells and ...creates a specific microenvironment. Here we report a novel biological property of CAFs and its cellular mechanism using in vivo and in vitro model. Cultured CAFs derived from human lung cancer tissue displayed significantly higher migration activity in response to PDGF-BB than that of fibroblasts from corresponding non-cancerous tissue (NCAFs). Moreover, KM104GFP (GFP-labeled human fibroblast cell line) co-cultured with human cancer cell line Capan-1 showed significantly higher migration activity than KM104GFP alone. No such phenomenon occurred when KM104GFP and Capan-1 were cultured separately. Even after KM104GFP were sorted from co-cultured Capan-1, KM104GFP retained their enhanced migration activity until passage-5 of culture in the absence of cancer cells. Despite a similar level of phosphorylation of ERK1/2 after exposure to PDGF-BB, the inhibitory effect of MEK inhibitor was significantly higher on migration of KM104GFP that had been sorted from co-cultured Capan-1 than of KM104GFP alone. This higher dependence on ERK1/2 signaling for cell migration was also seen in CAFs obtained from cancer tissue. The results of this study indicate that by association with cancer cells, CAFs can acquire enhanced migration activity which could be kept after separation from cancer cells and suggest the possibility that higher dependence on ERK1/2 signaling for enhanced migration activity would be one of the biological properties of CAFs.
Carbonic anhydrase (CA) IX catalyzes the hydration of carbon dioxide into carbonic acid and participates in a variety of physiological and biological processes. The aim of this study was to evaluate ...the prognostic significance of CA IX expression in patients with lung adenocarcinoma. Standard immunohistochemical techniques were used to study CA IX expression in 134 patients who underwent curative resection for adenocarcinoma of the lung at our hospital between January 1995 and December 1996. We evaluated the correlations between CA IX expression levels on cancer cells and clinicopathological factors. CA IX expression was not observed in normal lung tissue or specimens from non-invasive adenocarcinomas. CA IX immunostaining was detected in 33 (24.6%) invasive adenocarcinoma cases. Poor differentiated histological phenotype (
p
=
0.0015), pathological stage (
p
=
0.0400), vascular invasion (
p
=
0.0009) and lymphatic permeation (
p
=
0.0050) were significantly related to CA IX expression. On univariate analysis, CA IX positive cases showed significantly shorter overall survival (
p
=
0.0083) and disease-free survival (
p
=
0.0122). In particular, the overall and disease-free survivals in stages I
+
II were significantly shorter in the CA IX positive than in the CA IX negative cases (
p
=
0.0269 and 0.0011, respectively). Our results suggest that CA IX expression is strongly associated with tumor progression and indicates a poor prognosis for patients with stages I
+
II lung adenocarcinoma.
Eg5 is a microtubule motor protein that functions in bipolar spindle assembly. We investigated the relationship between Eg5 expression and the response to chemotherapy of patients with advanced ...non-small cell lung cancer (NSCLC).
Eg5 expression was investigated immunohistochemically in 122 formalin-fixed tumor samples from untreated stage IIIB or IV NSCLC patients. We also investigated cyclin B1 expression, which is involved in the G2/M transition. All patients received antimitotic agents combined with platinum chemotherapy. The response to chemotherapy was compared in relation to Eg5 and cyclin B1 expression and in relation to clinicopathological factors.
The response rate to chemotherapy of patients with Eg5-positive tumors was 37%, as opposed to 10% for patients with Eg5-negative tumors, and Eg5 expression was significantly associated with the response to chemotherapy (
P
=
0.002). The response rate of patients with cyclin B1-positive tumors (53%) was higher than that of patients with cyclin B1-negative tumors (23%) (
P
=
0.009), and Eg5 expression was significantly correlated with cyclin B1 expression (
P
=
0.005). A multivariate analysis confirmed Eg5 status to be an independent variable related to response to chemotherapy (
P
=
0.008).
Eg5 expression can predict a response to antimitotic agents combined with platinum chemotherapy among patients with advanced NSCLC.
What's known on the subject? and What does the study add?
It is known that a prostate cancer gene 3 (
PCA
3) urine assay is superior to serum
PSA
level or
PSA
‐related indices for predicting a ...positive biopsy result in European and
US
men.
This is the first report on
PCA
3 in a large cohort of
J
apanese men. The diagnostic value of the
PCA
3 score in
J
apanese men was similar to those reported in
E
uropean and
US
men. The study concludes that a combination of
PSA
density and
PCA
3 score may be useful for selecting patients who could avoid an unnecessary biopsy.
Objective
To examine the diagnostic performance of the prostate cancer gene 3 (
PCA
3) score for prostate cancer in
J
apanese men undergoing prostate biopsy.
Patients and Methods
This
J
apanese, multicentre study included 647
A
sian men who underwent extended prostate biopsy with elevated prostate‐specific antigen (
PSA
) and/or abnormal digital rectal examination (
DRE
).
Urine samples were collected after
DRE
.
The
PCA
3 score was determined using a
PROGENSA PCA
3 assay and correlated with biopsy outcome. Its diagnostic accuracy was compared with that of serum
PSA
level, prostate volume (
PV
),
PSA
density (
PSAD
), and free/total
PSA
ratio (f/t
PSA
).
Results
A total of 633 urine samples were successfully analysed (the informative rate was 98%). Median
PSA
was 7.6 ng/m
L
.
Biopsy revealed cancer in 264 men (41.7%). The
PCA
3 score for men with prostate cancer was significantly higher than that for men with negative biopsies (median
PCA
3 score: 49 vs. 18;
P
< 0.001). The rate of positive biopsy was 16.0% in men with a
PCA
3 score of <20 and 60.6% in those with a
PCA
3 score of ≥50.
Using a
PCA
3 score threshold of 35, sensitivity and specificity were 66.5 and 71.6%, respectively.
The area under the curve of the
PCA
3 score was significantly higher than that of the f/t
PSA
in men with
PSA
4–10 ng/m
L
(0.742 vs 0.647;
P
< 0.05).
In men with
PSAD
< 0.15 and
PCA
3 < 20, only three (4.2%) out of 72 men had prostate cancer.
Conclusions
The
PCA
3 score was significantly superior to f/t
PSA
in predicting a positive biopsy result for prostate cancer in
J
apanese men with
PSA
4–10 ng/m
L
.
The combination of
PSAD
and
PCA
3 score may be useful for selecting patients who could avoid an unnecessary biopsy.
A resected esophagus with numerous heterotopic sebaceous glands was examined in an attempt to determine whether esophageal heterotopic sebaceous glands are the result of a metaplastic process or a ...congenital anomaly. The present case concerns a 79‐year‐old Japanese man with numerous esophageal heterotopic sebaceous glands accompanied by superficial esophageal cancer. The resected esophagus possessed numerous heterotopic sebaceous glands, which could be seen clearly as slightly elevated, yellowish lesions. Histological examination of these glands, all of which were located in the lamina propria, revealed lobules of cells that showed characteristic sebaceous differentiation. Bulbous nests of proliferating basal cells showing sebaceous differentiation were occasionally observed in the esophageal epithelium. Of the antibodies against six different keratins used, only anti‐keratin 14 labeled both the heterotopic sebaceous glands and the bulbous nests. Acquired metaplastic change of the esophageal epithelium is probably the pathogenetic mechanism involved in these unusual lesions.
The most characteristic feature of the pathology of head and neck cancer is the various histological malignancies in various organs in head and neck. Last year, the 4th edition of General Rules for ...Clinical Practice and Pathology in Head and Neck Cancer in Japan was published. Since more than 80% of malignancies in the head and neck region are squamous cell carcinoma, the new rules describe the following items: 1) Macroscopic and microscopic findings, 2) Judgment of surgical and frozen section, 3) Intraepithelial neoplasma and dysplasia and 4) Superficial lesions of squamous cell carcinoma in the head and neck region. The present paper explains the new general rules for pathology of head and neck cancer focusing on the above items to add useful information for head and neck surgeons and oncologists.
To elucidate additional phenotypic differences between large cell neuroendocrine carcinoma (LCNEC) and small cell lung carcinoma (SCLC), we performed tissue microarray (TMA) analysis of surgically ...resected LCNEC and SCLC specimens. Immunostaining with 48 antibodies was scored based on staining intensity and the percentage of cells that stained positively. Four proteins were identified as significantly expressed in LCNEC as compared with SCLC: cytokeratin (CK)7, 113 vs 49 (P < .0301); CK18, 171 vs 60 (P < .0008); E-cadherin, 77 vs 9 (P < .0073); and beta-catenin, 191 vs 120 (P < .0286). Immunostaining of cross-sections containing LCNEC and SCLC components revealed significant expression of CK7, CK18 and beta-catenin in the LCNEC component compared with the SCLC component in 2 of 3 cases. Our results indicate that significant expression of CK7, CK18, E-cadherin, and beta-catenin is more characteristic of LCNEC than of SCLC, and these findings provide further support that these tumor types are separate entities morphologically and immunophenotypically, if not biologically.
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