Evidence for Diverse Prognosis in High-Grade Serous Ovarian Carcinoma: Solid, Pseudoendometrioid, and Transitional-Like; So-Called “SET Morphology” and Progesterone Receptor Status
Halit UNER1, Metin DEMIR2, Dincer GOKSULUK3, Ayse KARS2, Meral UNER1, Alp USUBUTUN1
1Department of Pathology, Hacettepe University School of Medicine, ANKARA, TURKEY
2Department of Medical Oncology, Hacettepe University School of Medicine, ANKARA, TURKEY
3Department of Biostatistics, Hacettepe University School of Medicine, ANKARA, TURKEY
Keywords: Epithelial ovarian cancer, Prognosis, Morphology, BRCA1, Immunohistochemistry
High-grade serous ovarian carcinoma (HGSC) is one of the major tumors of the gynecological system with a poor survival rate and
variable microscopic appearance. It was suggested that SET (solid, pseudo-endometrioid and transitional-like) morphology in ovarian HGSC is
predictably associated with BRCA deficiencies. In this study, we investigated the microscopic patterns and some immunohistochemical markers
predicting the prognosis of serous carcinoma.
Material and Method: We re-evaluated 305 HGSC ovarian resections morphologically and calculated the SET morphology percentages for each
case. Morphological and immunohistochemical data correlated with the survival and post-treatment disease progression data.
Results: The median age at diagnosis was 57 years and the median follow-up period was 3.1 years. The median overall survival (OS) of ovarian
carcinoma in SET-predominant tumors (n=60) was 81 months, while for tumors with SET non-dominant morphology (n=63) and non-SET
morphology (n=182) it was 59.7 and 44.7 months, respectively.
Conclusion: Predominant (more than 50%) SET morphology was significantly associated with increased survival rates of HGSC.
Immunohistochemically, p53, ERCC1, ER, and PR antibodies were applied and only PR antibody positivity was found to be associated with
borderline statistical significance for increased survival rates. Our results suggest that SET morphology may be a potential predictive and
prognostic marker in managing the treatment strategies of HGSC.
Ovarian cancer is associated with a high mortality rate
among women 1
. More than 70% of ovarian cancers
are diagnosed at an advanced stage and the absence of
an accepted early diagnostic method is one of the main
reasons for the increased mortality. The World Health
Organization (WHO 2020) has classified epithelial
ovarian tumors according to the cell of origin, and serous
carcinomas have been separated into low- and high-grade
. Approximately 90% of ovarian cancers are
epithelial in origin and serous carcinomas comprise the
Previous theories have suggested that ovarian cancers arise
from ovarian surface epithelium derivatives like inclusion
cysts, etc. 4,5. However, advanced sampling methods of
fallopian tubes in prophylactic salpingo-oophorectomy
materials obtained from BRCA mutated hereditary ovarian
cancer syndrome patients have radically changed our traditional beliefs 6. Early intraepithelial carcinomas are
reported at a fallopian tube location in BRCA deficient
patients and currently, it is widely accepted that the
majority of high-grade serous carcinomas (HGSCs) are
tubal in origin. Approximately 10% of HGSC develop via
BRCA1/BRCA2 mutations and the lifetime risk of ovarian
cancer in BRCA mutated patients is around 50% 7.
Recently Howitt et al. have reported that the coincidence
of intraepithelial lesions (serous tubal intraepithelial
carcinoma - STIC) is relatively rare in BRCA mutated serous
carcinomas (30%), while sporadic HGSCs may contain up
to 60% of tubal precursor lesions 8,9. The difference
between these tumors is not only limited to the presence
of precursor lesions but there are also various morphologic
features concerned. Soslow et al. have reported that the
morphologic appearance of HGSC in patients with BRCA
abnormality differs from the morphologic appearance of
those without this abnormality and called the morphologic
appearance of BRCA mutated patients as SET 10. This morphology consisted of appearances as “Solid”, “pseudo-
Endometrioid”, and “Transitional cell carcinoma-like”
patterns. They found that these morphologic patterns
are more common in patients with BRCA abnormalities,
and suggested that this indicates a potential relationship
between morphology and genotype.
There are few prognostic studies in BRCA mutated patients
with ovarian serous carcinoma, and two recent studies
suggest that these patients may have better survival 11,12.
Theoretically, the BRCA mutated group is more sensitive
to DNA crosslinking agents such as platinum-based
chemotherapeutics due to a lack of DNA repair mechanism
of the BRCA gene. However, eventually almost all highgrade
serous carcinomas develop resistance to platinum
13. Increased metabolism of platinum and efflux of
platinum or increased repair of platinum-induced DNA
cross-links are possible mechanisms of resistance. Repair
of platinum-induced DNA cross-links could be possible
with excision of nucleotides primarily by excision repair
cross-complementation 1 (ERCC1) and other nucleotide
The objective of this study was to investigate the effect of
SET morphology on clinical outcome and expression of
certain proteins such as p53, ER, PR, and ERCC1 in patients
with tubo-ovarian high-grade serous carcinoma.
The study was approved by the Hacettepe University
non-interventional Clinical Research Ethics Committee
(approval number: GO 15/454-26). The pathology reports
of patients diagnosed as “serous carcinoma of the ovary”
between 2001 and 2015 were searched from the hospital
information system of Hacettepe University Medical
School. Four hundred sixty-seven patients were found with
this diagnosis in our pathology files. Seventy-one cases
were consultation cases and we did not have their paraffin
blocks. There were 68 recurrent cases where the primary
operation was not performed in our institution. Both
patient cohorts were excluded, respectively, due to inability
of additional laboratory studies and possible morphologic
alterations following treatment. The slides of the remaining
cases were retrieved from the archive and re-examined by
two pathologists (AU, HU). After reviewing the selected
cases according to the WHO 2020 criteria, 23 samples were
found to have different morphologies than HGSC such as
low-grade serous carcinoma, borderline serous tumors, etc.
After excluding these cases, 305 ‘high-grade serous ovarian
carcinoma’ cases were included in the study.
By microscopic examination of all the slides of a given
case, invasive tumor patterns were noted while blinded
to the clinical outcome. The latest WHO bluebook
practically describes the morphological patterns of HGSC
as papillary, glandular, slit-like glandular, and cribriform.
We determined the detailed patterns of high-grade
serous carcinoma as follows. Papillary; neoplastic cells
covering central fibrous cores, one of the most common
conventional patterns. Micropapillary; composed of nonepithelial
lined spaces filled with solid tumor islands and
neoplastic cells usually devoid of fibrovascular cores.
Infiltrative; haphazardly distributed solid masses or less
condensed tumor cells forming slit-like spaces. Infiltrating
tumor masses were usually concomitant with stromal
desmoplasia. Solid; the presence of bulky tumor islands
without a specific growth pattern. Pseudoendometrioid;
tumor cells forming gland-like structures with usually
tubular cells, and also includes round spaces reminiscent of
cribriform architecture. Transitional; the presence of tumor
cells forming insular or trabecular architecture resembling
the multilayered epithelium of bladder (Figure 1A-F).
Morphologies like papillary, micropapillary, and infiltrative
pattern were more commonly observed and included in
the conventional pattern 14. Recently described solid,
pseudo-endometrioid, and transitional architectures were
noted and graded as follows; tumors having less than 5%
SET pattern (non-SET), tumors with more than 5% but
less than 50% SET morphology (SET non-dominant),
and tumors with more than 50% SET morphology (SETpredominant).
Besides, all fallopian tube sections were
evaluated for serous tubal intraepithelial carcinoma or
tumor infiltration and also for other disorders. Fallopian
tube sampling at our institution has improved over the
years. Before 2008, transverse sections from the isthmic
portion were submitted. However, from 2008 onwards,
the fimbrial portion of the fallopian tube was added to
the sampling in accordance with the guidelines. Because
of the retrospective nature of the study, and the variable
fallopian tube sampling at our institution, almost none of
the sampling has been performed with the sectioning and
extensively examining the fimbria (SEE-FIM) protocol,
unless there was strong evidence that a patient could have
Figure 1: Architectural patterns of high-grade serous carcinoma (H&E, X40). A) Papillary pattern. B) Micropapillary pattern. C) Infiltrative pattern. D) Solid pattern. E) Pseudoendometrioid pattern. F) Transitional pattern.
Two foci were marked on the tumor slides and 3 mm samples
were removed from the formalin-fixed paraffin-embedded
tissue blocks to construct tissue microarray (TMA) blocks.
If SET morphology was encountered within the tumor, at least one focus was sampled from that particular area.
Several 4-5 micrometer thick sections obtained from TMA
blocks were stained with hematoxylin and eosin (H&E)
and immunohistochemical staining was performed on the
Leica BOND-MAX IHC/ISH automated immunostainer
using the following commercial antibodies; ER (Biocare;
EDTA 1/50; 6F11), PR (Biocare; EDTA 1/100; SP2), p53
(Biocare; EDTA 1/200; DO-7) and ERCC1 (Biocare; EDTA
Evaluation of Immunohistochemical Results
We used the College of American Pathologists Guideline
recommendations for ER and PR immunohistochemistry,
and at least 1% positive tumor cell nuclei was accepted as
the threshold for a positive assay (15). Completely negative
staining with p53 or overexpression in more than 80% of
tumor cell nuclei widely known as ‘all or nothing’ indicating
aberrant expression was accepted as “mutant” (16). Other
staining patterns were included in ‘wild-type’ for p53. The
staining intensity for ERCC1 was graded on a scale from
0 to 3 (a higher number indicating higher intensity) and
the percentage of positive tumor cell nuclei was calculated
according to the study by Park et al. 17.
Demographic, clinical, and survival parameters were
recorded from the hospital registration system. Overall survival (OS) information was also checked from the
National Death Notification System. The time between
the last cycle of first-line chemotherapy and the first cycle
of the second-line chemotherapy was defined as time to
progression (TTP). The duration from the operation date
to the starting date of the first non-platinum chemotherapy
was accepted as time to first platinum-free chemotherapy
Data analysis was performed using the IBM SPSS software,
version 21. Numerical variables were summarized using
the mean and standard deviation or median and quartiles
depending on the normality of the underlying distribution.
The normality assumption was assessed using graphical
(Q-Q plot, histogram, etc.) and analytical methods
(Shapiro-Wilk’s normality test). Categorical variables
were summarized with frequencies and percentages.
Demographic variables were compared between SET
morphology groups using chi-squared tests (e.g., Pearson,
Fisher exact, etc.) for categorical variables and independent
samples hypothesis tests (e.g., Student’s t-test or Mann-
Whitney U test) for numerical variables, based on the
normality of data. The effect of ER, PR, ERCC1, and SET
morphology on survival was investigated using the Kaplan-
Meier method and log-rank test. Survival times were
reported using median times along with 95% confidence intervals. Pairwise comparisons were evaluated using
Bonferroni adjusted p-values, and indicated with superscript
letters. Groups not sharing similar letters are expressed as
pairwise significant. Univariate Cox regression was used to
find a list of possible risk factors regarding mortality, and
pathologic features identified with univariate analyses were
further entered into the multivariate Cox regression model
to determine independent predictors of survival adjusted
for the remaining risk factors. All test results were evaluated
using two-sided p-values at the 0.05 level of significance.
The median age at diagnosis was 57 years (range 30-91).
The tumor presented as a bilateral ovarian mass in 255
cases (83%). In 182 cases (60%), conventional serous
morphology was completely dominant (only minuscule
or no SET morphology), so-called non-SET. In 123 cases
(40%), varying amounts of SET morphology were recorded
(more than 5% of the tumor). In about half of these cases
(60 cases) the SET morphology was more than 50%, socalled SET-predominant. In the rest of the cases (63 cases),
SET morphology was between 5% and 50%, which was
called SET non-dominant (Table I
Click Here to Zoom
|Table I: Patient demographics, stage, immunohistochemistry results and survival period based on morphology.
Fallopian tubes were free of tumor in 144 cases (47%).
The tubes were infiltrated by the tumor in 119 (39%) of
the remaining 161 cases. Only 42 cases (14%) were positive
for intraepithelial lesion (STIC) in the fallopian tubes,
and 23 of them had non-SET morphology while 19 had
SET morphology. Even though we found no statistical
significance, the overall survival time of patients with
tumor-free fallopian tubes was 4 months longer compared
to cases with a precursor lesion or tumor in tubal tissues, 43
versus 39 months respectively.
Eighty-two percent of the patients (249/305) had stage III
disease according to the 2014 FIGO Staging System at the
time of diagnosis. The distribution of stages was similar in
the SET and non-SET morphology groups. Patients whose
tumors had SET morphology were 2 years younger at the
time of diagnosis compared to non-SET HGSCs but this
difference was also not statistically significant (Student’s
t-test, p = 0.12).
The mutant type staining pattern of p53 was seen in 301
cases (99%) (Figure 2A,B). Wild-type staining was observed
in four cases only (Table I, Figure 2C). Two had SETpredominant
morphology, while the other two had serous
cancer with non-SET morphology. We included these cases
in the study because of the presence of complex papillary
structures, solid pattern, stratification of glandular cells,
marked atypia, and high mitotic rates of conventional
Figure 2: Immunohistochemistry. A) Diffuse strong nuclear staining with p53 (mutant). B) Total loss of expression for p53 (aberrant staining) that is also considered as mutant. C) Focal staining consistent with wild-type p53 expression. D) Higher ER positivity is usually seen in the diffuse pattern. E) PR expression is often seen as focal staining. F) High expression of ERCC1 (60% of cells stained as 2+).
Hormone receptor expression (ER and/or PR) was
present in 269 cases (88%); 36 patients had no hormone
receptor expression. ER expression was detected in 266
cases (87%) and PR expression in 60 (20%) cases (Figure
2D,E). The majority of the tumors expressed ERCC1 (Figure 2F), and only 15 cases (5%) out of 305 were ERCC1
negative. No significant correlation was found between the
immunohistochemical markers and microscopic tumor
patterns (Pearson’s chi-square, p = 0.79).
Survival Data by Morphology
The median follow-up period was 3.1 years (range 0.1 -
12.5 years). One hundred fifty-nine patients had died, and
86 patients were still alive. The follow-up data of 245 cases
were available, and that of the remaining 60 patients were
missing. The ratio of patients who had progressive disease
was 85% (n=259). Platinum resistance developed in 73%
of patients. Platinum with or without taxane regimens
were used in 81.6% of the patients as first line. The
median number of chemotherapy lines administered was 2
(minimum: 0 - maximum: 11).
The median OS of high-grade serous carcinomas in non-
SET (conventional) morphology and tumors with SET
non-dominant morphology was 44.7 and 59.7 months,
respectively, while the median OS of SET-predominant
tumors was 81 months. The presence of SET morphology
was a predictor of improved clinical outcome in OS
analysis (p=0.005). Post-hoc analyses showed that the SET-predominant group had significantly higher median OS
compared to conventional histology (p=0.004) (Figure 3A,
Click Here to Zoom
|Figure 3: Survival analysis of the HGSC morphology groups; A) Overall
survival rates of non-SET (blue), SET non-dominant (green), and SETpredominant
(yellow) separately. B) Overall survival rates of non-SET
(blue) versus SET non-dominant & SET-predominant (green) together.
C) Overall survival rates of non-SET & SET non-dominant together
(blue) versus SET-predominant (green). D) Time to progression (TTP).
E) Time to first platinum-free chemotherapy (TTFPFC).
SET-predominant and non-dominant groups together had
a significantly higher OS compared to the non-SET group
(67.4 months vs. 44.7 months, p = 0.003) (Figure 3B).
The SET-predominant group had a better outcome in
terms of OS compared to SET non-dominant and non-SET
tumors together, and this was statistically significant (81
months vs. 46.7 months, p = 0.006) (Figure 3C).
In the entire cohort, the median overall survival (OS),
median TTP and median TTFPFC were 50.4; 21.5, and 40
months, respectively. All these survival parameters showed
only statistical significance between morphologic patterns.
Median TTP for non-SET high-grade serous carcinomas,
SET non-dominant, and SET-predominant groups were
16.9; 23.8, and 48.6 months, respectively (p=0.013).
According to posthoc analyses, the SET-predominant group
showed significantly higher median TTP compared to both
the SET non-dominant (p=0.028) and non-SET groups
(p=0.026) (Figure 3D, Table I). Median TTFPFC for non-
SET high-grade serous carcinomas, SET non-dominant,
and SET-predominant groups were 27.5; 50.4, and 77.7
months, respectively (p=0.003). The SET-predominant
group had a higher median TTFPFC compared to the non-
SET group with statistical significance (p=0.002) (Figure 3E). The presence of SET morphology was a predictor of
improved clinical outcomes for all survival parameters.
Survival Data by Immunohistochemistry
The median OS of PR positive and negative cases were 66.8
months and 46.3 months respectively. This difference had
a borderline statistical significance (p=0.059) (Table II). ER
expression, unlike PR, did not confer a survival advantage,
and the overall survival in ER-positive and negative cases
was 54 and 47 months, respectively.
Click Here to Zoom
|Table II: Univariate and multivariate Cox regression models of survival time.
In 152 cases with high and 153 cases with negative and
low ERCC1 expression, median OS was 49 months and 51
months, respectively. The difference was not statistically
significant. Median TTP for the low and high ERCC
groups was 35.6 (95% CI: 9.7-61.4) and 19.3 (95% CI: 14.8-
23.8) months, respectively, and this difference was not
statistically significant (p=0.27). Median TTFPFC for the
same groups was 42.3 (95% CI: 34.8-49.7) and 34.4 (95%
CI: 20.5-50.3) months, respectively (p=0.54).
In 4 cases who had wild-type staining p53, median OS was
47 months while in those with aberrant staining it was 41
months. There was no significant correlation between p53
staining and survival.
In the Cox regression analysis for OS, PR positivity
was a positive factor for survival time (RR=0.64; 95%
CI:0.42-0.96; p=0.031). SET predominance showed a
decreased death risk compared to non-SET high grade
serous carcinomas (RR=0.47; 95% CI:0.3-0.74, p=0.001).
However, only SET predominance remained as the unique
independent predictor of prevention from progression
and platinum resistance compared to non-SET high grade
serous carcinomas (RR for progression=0.47; 95% CI:0.28-
0.79; p=0.004 and RR for platinum resistance=0.4; 95%
CI:0.24-0.68; p=0.001) (Table II).
By reviewing a relatively large set of high-grade serous
carcinomas, diagnosed according to WHO 2020 criteria,
we demonstrated that these tumors could be potentially
heterogeneous not only by their genetic and IHC profile
but also by their morphological pattern and prognostic
surveillance. In particular, increased interest in patients
with high-risk hereditary cancers led to an increased
understanding of the pathogenesis and morphological
spectrum of serous cancers. In 2006, early tubal
carcinomas were considered as precursors of high-grade
serous carcinomas, and later in 2012, patients with BRCA
mutations were found to have a different morphology
such as SET (solid, pseudo-endometrioid, transitional
carcinoma-like) compared to classical serous papillary
carcinomas, and recently in 2015, lesser precursor lesions
were reported in tumors with a BRCA mutation, leading
to the opinion that serous carcinomas may reflect a more
heterogeneous neoplastic development rather than a
homogenous tumor group 6,9,10
Based upon studies following risk-reducing salpingooophorectomy
that detected serous carcinoma precursors
in the fimbria of individuals with BRCA mutation, it
was proposed that serous carcinoma originated in the
fallopian tubes. These studies suggested that serous tubal
intraepithelial carcinoma (STIC) was the prototype of
serous carcinoma precursor. However, the detection
rate of STIC in these individuals remained low. In early
studies, STIC was reported in 10% of patients with BRCA
mutation but in recent studies this rate goes up to 30%
with a detailed sampling of the fimbrial end (9, 18). On
the other hand, the prevalence of STIC in sporadic highgrade
serous carcinomas is around 60% 8. The majority of BRCA mutations are located in the BRCA1 gene and the
BRCA2 gene mutations comprise fewer cases and the latter
also demonstrates a smaller risk for early fallopian tube
HGSCs are the most common ovarian neoplasm in women
with BRCA 1 and 2 mutations and there are numerous
studies on this topic. BRCA1 and BRCA2 mutation rates
reported as 10% of serous carcinomas earlier, increased up
to 40% in recent publications 20,21. Contrary to BRCA,
the incidence of SET morphology in serous carcinomas is
not well known yet. In our study, 123 (40%) of 305 highgrade
serous carcinoma cases showed SET morphology.
These patients were 2 years younger than the patients
with conventional morphology and, cases with SET were
detected marginally more frequent at an early stage. The
difference between the rates of STIC in SET and non-SET
tumors was not notable. While cases with SET morphology
in our study group were consistent with literature for age at
presentation, the rate of STIC detection in these tumors was
similar to that in conventional carcinomas. This difference
might be due to fewer samples taken in the past at our
institution during sampling procedures compared to the
detailed SEE-FIM method and this may have caused very
early precursor lesions to be missed in conventional cases.
The molecular detection of BRCA mutation is
clinicopathologically useful since it is predictive for
relatively good chemotherapy response with comparably
higher survival and a possible different microscopic
appearance 22,23. Unfortunately, we did not have a
chance to confirm the BRCA mutation further by PCR or
by IHC in our cohort.
In breast cancer, the relationship between hormone
expression profile and prognosis has been extensively
studied, and classifications based on hormone receptor
expression profile, are widely used in tumor management
24. Estrogen causes proliferation through cellular
transforming molecules like the IL-6/STAT-3 signaling
pathway 25. On the contrary, the progesterone-receptor
induced by ER activation is known to induce apoptosis,
and behaves as a tumor suppressor protein by activation
through cellular caspase-8 26. The protective effect of
pregnancy on ovarian cancer is thought to be due to high
levels of progesterone during pregnancy. Improved survival
in ovarian cancer with positive estrogen or progesterone
receptors has been reported in a few studies 27,28. In
our study, the median OS of PR positive and negative
cases were 66.8 months and 46.3 months respectively. ER
expression did not confer a survival advantage such as
PR, and the overall survival in ER-positive and negative cases were 44 and 37 months respectively. There was no
relationship between PR expression and the morphological
appearance of the tumor; however, it can be postulated
that tumors expressing PR reflect a different high-grade
serous carcinoma group and could benefit from endocrine
treatment due to improved prognosis.
The prognostic value of ERCC1 expression in gynecological
and non-gynecological cancers and its association with
chemotherapy resistance have been investigated by
various groups 29-32. Although studies are reporting
that high ERCC protein expression predicts resistance to
platinum-based therapies in various tumors, there is no
general agreement on this issue 33-36. The relationship
between ERCC1 IHC and survival in our study revealed
a non-significant result, and the group with high ERCC1
expression was found to have 2 months shorter survival
compared to the low ERCC1 expression group. In our
patient population, there was no significant difference for
TTP and TTFPFC among ERCC1 groups. Therefore, we
could not demonstrate a predictive role of ERCC1 levels
for platinum resistance in ovarian cancer.
The frequency of p53 mutation in high-grade serous
carcinoma is about 99% and can be detected by
immunohistochemistry as overexpression or complete
absence that indicates gain-of-function or loss-of-function,
respectively 37. In our study, 301 (99%) cases showed
one of these two staining patterns consistent with the
p53 mutation. Wild-type p53 was detected in only 4
cases. There was no significant difference in survival rates
between patients with wild-type p53 staining and cases
with aberrant staining. To summarize, wild-type p53
staining can be detected in high-grade serous carcinomas,
although extremely rare, but a detailed morphological and
immunohistochemical examination should be performed
to exclude other epithelial tumors of the ovary in cases of
In this study, the median OS of serous carcinoma with
non-SET morphology was calculated as 44.7 months while
the value for serous carcinoma with any SET morphology
was calculated as 67 months. Moreover, the 21 months
longer OS period in SET predominant tumors compared
to SET non-dominant tumors suggests that high-grade
serous carcinomas could be potentially diverse. There
are 2 publications in the current literature discussing the
relationship between the morphological appearance and
the prognosis of high-grade serous carcinomas. In one
of these, SET morphology and chemotherapy sensitivity
were correlated. Howitt et al. primarily focused on SET,
BRCA, and STIC relationships in a relatively small patient population (n=58) and reported a better clinical outcome
for tumors with SET morphology in their cohort compared
to classical morphology 9. Our results are similar with
tumors having larger SET morphology areas having better
TTP and TTFPFC in our study. In the second study,
Ritterhause et al. assessed 104 patients’ survival outcomes.
They showed a strong relationship with non-classic serous
carcinoma histology and BRCA1 mutations but their
groups of classic and SET morphologies did not show
any significant difference for progression-free survival,
platinum sensitivity, and OS 38.
In our study, higher ERCC1 was not associated with
platinum resistance but higher SET morphology was
associated with platinum sensitivity as reflected with
a trend toward higher platinum-free survival. SETpredominant
and the conventional serous morphology
groups had 77.7 and 27.5 months of median TTFPFC,
respectively (p=0.002). SET comes out as a new predictive
factor for platinum sensitivity according to our findings.
Moreover, PR positivity was protective from death only but
SET predominance was the single independent predictive
factor of protection in all of the survival endpoints.
A potential limitation of our study is that we were not able
to test for the BRCA mutation or even other homologous
recombination-deficiencies for corresponding tumor
patterns. Additionally, due to the retrospective nature of
the study, we were unable to elaborate in-situ lesions in
ancient cases. However, the abundant number of cases and
adequate follow-up periods may hinder these limitations.
Mounting evidence in recent reports supports that SET
morphology has a genetic background different from
classical serous morphology and lacks precursor lesions.
A better understanding of the molecular pathogenesis of
SET morphology will guide future efforts in diagnosis,
biomarker-supported classification algorithms, and
treatment strategies of high-grade serous ovarian
CONFLICT OF INTEREST
Study was funded by Hacettepe University Scientific
Research Unit (THD-2015-8349). The authors declare no
potential conflict of interest.
Concept: AU, AK, Design: AU, HU, AK, Data collection or
processing: HU, MD, MU, DG, Analysis or Interpretation:
AU, HU, AK, Literature search: HU, MD, Writing: HU,
MD, DG, AK, MU, AU, Approval: HU, MD, DG, AK, MU,
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