14 research outputs found
Decreased D2-40 and increased p16INK4A immunoreactivities correlate with higher grade of cervical intraepithelial neoplasia
<p>Abstract</p> <p>Background</p> <p>D2-40 has been shown a selective marker for lymphatic endothelium, but also shown in the benign cervical basal cells. However, the application of D2-40 immunoreactivity in the cervical basal cells for identifying the grade of cervical intraepithelial neoplasia (CIN) has not been evaluated.</p> <p>Methods</p> <p>In this study, the immunoreactive patterns of D2-40, compared with p16<sup>INK4A</sup>, which is currently considered as the useful marker for cervical cancers and their precancerous diseases, were examined in total 125 cervical specimens including 32 of CIN1, 37 of CIN2, 35 of CIN3, and 21 of normal cervical tissue. D2-40 and p16<sup>INK4A </sup>immunoreactivities were scored semiquantitatively according to the intensity and/or extent of the staining.</p> <p>Results</p> <p>Diffuse D2-40 expression with moderate-to-strong intensity was seen in all the normal cervical epithelia (21/21, 100%) and similar pattern of D2-40 immunoreactivity with weak-to-strong intensity was observed in CIN1 (31/32, 97.2%). However, negative and/or focal D2-40 expression was found in CIN2 (negative: 20/37, 54.1%; focal: 16/37, 43.2%) and CIN3 (negative: 22/35, 62.8%; focal: 12/35, 34.3%). On the other hand, diffuse immunostaining for p16<sup>INK4A </sup>was shown in 37.5% of CIN1, 64.9% of CIN2, and 80.0% of CIN3. However, the immunoreactive pattern of D2-40 was not associated with the p16<sup>INK4A </sup>immunoreactivity.</p> <p>Conclusions</p> <p>Immunohistochemical analysis of D2-40 combined with p16<sup>INK4A </sup>may have a significant implication in clinical practice for better identifying the grade of cervical intraepithelial neoplasia, especially for distinguishing CIN1 from CIN2/3.</p
The potential role of podoplanin in tumour invasion
Podoplanin is a small mucin-like transmembrane protein, widely expressed in various specialised cell types throughout the body. Here, we revisit the mechanism of podoplanin-mediated tumour invasion. We compare molecular pathways leading to single and collective cell invasion and discuss novel distinct concepts of tumour cell invasion
How useful is the assessment of lymphatic vascular density in oral carcinoma prognosis?
Abstract
Background
Lymphatic vessels are major routes for metastasis in head and neck squamous cell carcinoma (HNSCC), but lymphatic endothelial cells (LECs) are difficult to recognize in tumor histological sections. D2-40 stains podoplanin, a molecule expressed in LECs, however, the potential prognostic usefulness of this molecule is not completely understood in HNSCC. We aimed to investigate the value of assessing peritumoral and intratumoral lymphatic vessel density (LVD) as prognostic marker for HNSCC.
Methods
Thirty-one cases of HNSCC were stained for D2-40 and CD31. LVD and blood vessel density (BVD) were assessed by counting positive reactions in 10 hotspot areas at ×200 magnification.
Results
D2-40 was specific for lymphatic vessels and did not stain blood vascular endothelial cells. LECs showed more tortuous and disorganized structure in intratumoral lymphatic vessels than in peritumoral ones. No statistical differences were observed between peritumoral-LVD and intratumoral-LVD or between peritumoral-BVD and intratumoral-BVD. Tumor D2-40 staining was positively associated with lymphatic vessel invasion (p = 0.011).
Conclusion
LVD is a powerful marker for HNSCC prognosis. We found significant differences in peritumoral and intratumoral D2-40 immunoreactivity, which could have important implications in future therapeutic strategies and outcome evaluation
Expression of podoplanin in the invasion front of oral squamous cell carcinoma is not prognostic for survival
Tumorigenic role of podoplanin in esophageal squamous-cell carcinoma
Background. Podoplanin, a mucin-type transmembrane
glycoprotein, is thought to be one of the cancer stem cell
markers for squamous-cell carcinoma of the vulva. The
objectives of the present study were to examine the role of
podoplanin in esophageal squamous-cell carcinoma
(ESCC).
Methods. Expression of podoplanin was examined immunohistochemically
in 61 cases of ESCC that had not been
treated with chemotherapy or radiotherapy before surgery.
Because cancer stem-cell quantities have been reported to
increase with chemotherapy and radiotherapy, cases in
patients who did not receive such prior therapies were
included in this study. Cases with[10% tumor cells showing
signals for podoplanin were categorized as podoplanin high,
and the others were classified as podoplanin low. The effects
of podoplanin on the behavior of cancer cells were evaluated
in ESCC cell lines in which podoplanin expression was
knocked down.
Results. To examine whether podoplanin could be used as
a cancer stem cell marker for ESCC, podoplanin-positive
and podoplanin-negative fractions were sorted separately
from the ESCC cell line and cultured. Podoplanin-positive
ESCC cells yielded both podoplanin-positive and podoplanin-
negative cells, whereas few cells were obtained from
podoplanin-negative ESCC cells. When podoplanin
expression was knocked down, ESCC cell lines became
vulnerable to anticancer drugs and showed defective
invasion and tumorigenic activities. Nineteen (31.1%) of
61 cases were categorized as podoplanin high. Podoplaninhigh
cases were correlated with T category, stage of disease,
lymphatic and vascular invasion, recurrence, and
prognosis of patients. Podoplanin-low cases showed better
overall and disease-free survival.
Conclusions. There is a role for podoplanin in tumorigenesis
and malignant progression in ESCC.
Cancer cells comprise a heterogeneous group of cells,
among which only a small population of cells possesses the
ability to reconstitute a whole tumor.1–3 This population,
called cancer stem cells (CSCs), efficiently forms colonies
in semisolid culture and is xenotransplantable in nonobese
diabetic/severe combined immunodeficiency (NOD/SCID)
mice.4 CSCs were first identified in leukemia and subsequently
isolated from solid tumors, such as those of breast,
brain, prostate, melanoma, colon, pancreas, head/neck,
liver, and gastric cancers.5–15 CSCs are known to be
resistant to chemotherapy and radiotherapy and are more
invasive than non-CSCs.
Recognition of CSCs and their efficient elimination may
be a valuable strategy for treatment of cancers. Therefore,
studies to search for markers of CSCs have been performed.
First, successful isolation of CD34? CD38-
leukemic stem cells was reported.5 However, subsequent
studies showed that markers for CSCs differ among cancers
originating from different organs. Atsumi et al. reported
that podoplanin, a mucin-type transmembrane glycoprotein,
is a possible candidate CSC marker for squamous-cell
carcinoma (SCC).16 Cultured cells from the SCC cell line
A431, which is derived from the vulva, consist of two
populations: podoplanin-positive and podoplanin-negative
cells. CSCs are known to produce both CSC and non-CSC