Discussion
Laryngeal cancer is most frequently seen between the 5. and 7. decades
of life in the world.1 Laryngeal cancers include 1.1%
of all malignancies worldwide and this rate is 1.9% in males, and 0.3%
in.4 The age average and gender ratio in our study was
in consistency with the literature.
Heat shock proteins are chaperon proteins that have a protective
function for the cell by normally creating an adaptation mechanism and
increasing against environmental and pathophysiological stressors, and
they make up an important step in the defense system. HSP70t and HSP70-2
(HSPA-2), unlike other HSP70 chaperon proteins, are expressed in the
testicular tissues and are not seen in other tissues or are rarely seen
in them.16 In a study conducted on rats, Zhu et. al.
stated that when they caused HSPA-2 defects, the primer spermatocytes
got stuck at meiosis I, and other HSPA proteins cannot compensate for
it. According to these results, they have argued that HSPA-2 is a
molecular chaperone for CDC2/cyclin B1 complex formation, and that their
interaction is necessary to ensure the G2/M-phase transition during
mitosis and meiotic cell cycles.17 In a different
study, it has been noted that the G1/S phase arrest occurred, and malign
cell proliferation decreased after the HSPA-2 gene was suppressed in the
lung adenocarcinomas. It was shown that after the HSPA-2 decreased; the
ERK1/2 cascade having functions such as cell survival rate,
proliferation stimulation, cell differentiation, cell aging and
apoptosis was affected.18
It has been reported that HSPA-2 is effective in many malignancy
carcinogenesis. While it is not expressed in normal tissues, it is
excessively expressed in malign cells.12 In our study,
HSPA-2 expression was only observed in the basal layer of adjacent
squamous epithelium not containing dysplasia in all of the cases. In
well-differentiated tumors expression was observed predominantly in the
periphery of tumor solid islands, and a more intense expression was
observed in a more diffused way in areas where differentiation loss was
distinct in tumors cells. A diffused and strong expression being
observed in moderately and poorly differentiated tumors while weak
staining seen in the adjacent epithelial basal and the periphery of
well-differentiated tumor islands have suggested that HSPA-2 might have
a role in tumor cell migration, invasion and carcinogenesis. Zhang et.
al. reported that while they did not observe staining with HSPA-2 in the
normal esophagus epithelial, they observed poor staining in areas
adjacent the tumor and squamous epithelium basal layer, and stronger
staining in infiltrative areas.13 In their study,
Scıeglnska et. al. reported observing positive HSPA-2 in keratinocytes
in the adjacent epidermis basal layer and in the infiltrative areas of
all the skin tumors. On the other hand, they reported observing positive
HSPA-2 in the infiltrative areas of half of their cases, while they did
not find positivity in the normal epithelium in areas adjacent the tumor
in the head and neck areas of SCC cases.12
A different point that we have observed in our study is to see important
differences regarding straining intensity and frequency in the low-grade
epithelial dysplasia and high-grade epithelial dysplasia areas of the
adjacent epithelium. In all of our cases in low-grade epithelial
dysplasia areas, positivity was found in only 1/3 of the basal part of
the epithelium, while a full coat staining was seen in high-grade
epithelial dysplasia areas. We think that while differentiating
epithelial dysplasia in laryngeal biopsies with this different staining
pattern, the HSPA-2 expression type can also be immensely helpful in
differential diagnosis immunohistochemically. No study has been
conducted in the literature on this subject, and we think that new
studies should be conducted with a larger number of cases.
In addition to HSPA-2 being excessively expressed in many types of
cancer, there are many studies showing that it has an effect on tumor
progression. It is indicated that tumor cells gain resistance against
apoptosis related to hypoxia with an increase of HSPA-2, and that is how
they stay alive.19 In our study, a significant
relationship was observed between the excessive expression of HSPA-2 and
important prognostic parameters such as the primary tumor,
lymphovascular invasion, lymph nodule metastasis, the TNM stage and
survival rate. Fu et. al. reported that histological grade, tumor
radius, clinical stage in hepatocellular carcinomas were directly
proportionate to HSPA-2, thus HSPA-2 can have a role in carcinogenesis,
tumor development, progression and metastasis. They indicated that they
found a significant negative correlation especially between survival
rate and HSPA-2 expression.15 In their study
emphasizing on esophagus SCC cases, Zhang et. al. stated that the
excessive expression of HSPA-2 was associated with the primary tumor,
clinical stage, lymph nodule metastasis and
recurrence.13 Garg et. al. have argued that HSPA-2
expression is related to cellular motility and growth, so HSPA-2 has a
role in cancer spread during the early stages. In their study on bladder
cancer, they stated that they observed a significant relationship
between the clinical stage, histological grade and HSPA-2
expression.11 In a different study conducted by Garg
et. al. on cervix cancer, they obtained similar results and indicated
that HSPA-2 had an effect on the progression of cervix
cancer.10 In their study, Zhai et. al. have noted that
HSPA-2 is related to a poor prognosis in tumor angiogenesis and
pancreatic adenocarcinoma, and has an important place in its
progression.9 Similar to our study, various studies
have shown that in cases where excessive expression of HSPA-2 is seen,
there are higher lymph nodule metastasis and therefore a worse
prognosis.11,20 In their study, Scıeglınska et. al.
found a significant relationship between HSPA-2 expression and the TNM
stage, histological grade and prognosis in Non-Small Cell Lung
Carcinomas. They have highlighted that especially in stage I and II
cases, high HSPA-2 expression is related to lower survival
rates.12 In their in vivo study using a mouse model,
Garg et. al. considered the matter from a different point of view and
stated that they decreased tumor growth rates by 75% with HSPA-2
inhibition in rats.10 When the results of our study
and the available data in the literature were evaluated, finding a
significant relationship between important prognostic parameters such as
the primary tumor, lymphovascular invasion, lymph nodule metastasis, the
TNM stage, survival rate suggested that this marker can be used in
prognosis in LSCC immunohistochemically.