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Paradoxically there was no Maspin detected in benign secretory cells (Pierson et al.,
2002). The pattern of intracellular distribution might be of consequence. Invasive
ovarian cancers tended to show high expression in the cytoplasm and high expres-
sion was seen in high tumour grade as compared with low malignancy tumours or
benign tumours and poor prognosis (Sood et al., 2002). But curiously transfection
of Maspin into ovarian cancer cell lines markedly reduced
in vitro
invasion. In these
early investigations inducible expression vectors were not used. Transfection of vec-
tors can produce collateral genetic activation. Recombinant Maspin was shown some
years ago to be able inhibit
in vitro
invasion and this effect was blocked by antibod-
ies raised against the RSL (Sheng et al., 1994). Solomon et al. (2006) found that
Maspin translocation into the nucleus correlated with suppression of angiogenesis
in ovarian serous carcinoma is associated together with VEGF expression. This is
not unexpected or remarkable
per se
. There are several examples where cytoplasmic
restriction of signalling ligands has affected biological function.
The presence of Maspin in the nucleus correlated with the expression of ER and
PR. In contrast, cytoplasmic Maspin correlated with the absence of ER/PR and large
S-phase fraction (Mohsin et al., 2003; Umekita et al., 2011). High Maspin expression
in the nucleus has correlated with good prognosis in NSCLC (Berardi et al., 2012).
Regrettably most studies have related to Maspin expression in tumour cell lines.
Whilst loss of expression in them is important and significant to the establishment of
a suppressor role for Maspin, many reports have subsequently cited them as if tumour
derived cell lines are ipso facto representatives of tumour tissues themselves.
So a cautionary discussion of contrary verdicts is warranted here. Several early
reports have indicated high Maspin expression in carcinomas. The tumour sup-
pressor role has been the subject of intense scrutiny ever since Maass et al. (2001)
detected its expression in 23/24 pancreatic cancers and also in high grade precancer-
ous lesions. Ogasawara et al. (2004) found Maspin was expressed more frequently in
undifferentiated and poorly differentiated than in well differentiated thyroid tumours.
Also follicular adenomas and normal thyroid tissues did not express Maspin.
Similarly it was expressed in invasive bladder cancer but not in tumour-free epithe-
lium (Sugimoto et al., 2004). Maspin was detected in a majority of gastric carcinoma
and also in foci of intestinal metaplasia (Akiyama et al., 2003); also in pancreatic
ductal adenocarcinomas where expression was however seen mainly in low grade
tumours (Ohike et al., 2003). Cytoplasmic staining was more frequent in stage III
than stage I NSCLC. Maspin mRNA levels were also higher in stage III disease than
in normal tissues. Poor survival corresponded with high Maspin expression (Hirai
et al., 2005). Yatabe et al. (2004) noticed Maspin expression due to reduced methyla-
tion in virtually all the squamous cell lung cancers they tested, whilst half the num-
ber of adenocarcinomas showed no Maspin expression. Maspin is expressed in both
the cytoplasm and nuclei of endometrial cancers (Li et al., 2007d) and papillary thy-
roid carcinoma (Shams et al., 2006). A recent study to this effect concerns TNBCs.
Umekita et al. (2011) have detected Maspin expression in nearly 9/10 of TNBC
cases and the expression was related to histological grade. Often investigations have
focused on either detecting epigenetic silencing or detection of the protein expres-
sion. Hypermethylation of the gene promoter is always shown to correlate with loss
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