J Pathol Transl Med.  2017 Sep;51(5):471-481. 10.4132/jptm.2017.06.02.

Diverse Immunoprofile of Ductal Adenocarcinoma of the Prostate with an Emphasis on the Prognostic Factors

• Jeong SU
• Kekatpure
• Park JM
• Han M
• Hwang HS
• Jeong HJ
• Go H
• Cho YM

• KMID: 2392566
• DOI: http://doi.org/10.4132/jptm.2017.06.02

Abstract

BACKGROUND
Ductal adenocarcinoma (DAC) of the prostate is an uncommon histologic subtype whose prognostic factors and immunoprofile have not been fully defined.
METHODS
To define its prognostic factors and immunoprofile, the clinicopathological features, including biochemical recurrence (BCR), of 61 cases of DAC were analyzed. Immunohistochemistry was performed on tissue microarray constructs to assess the expression of prostate cancer-related and mammalian target of rapamycin (mTOR) signaling-related proteins.
RESULTS
During the median follow-up period of 19.3 months, BCR occurred in 26 cases (42.6%). DAC demonstrated a wide expression range of prostate cancer-related proteins, including nine cases (14.8%) that were totally negative for pan-cytokeratin (PanCK) immunostaining. The mTOR signaling-related proteins also showed diverse expression. On univariate analysis, BCR was associated with high preoperative serum levels of prostate-specific antigen (PSA), large tumor volume, predominant ductal component, high Gleason score (GS), comedo-necrosis, high tumor stage (pT), lymphovascular invasion, and positive surgical margin. High expressions of phospho-mTOR (p-mTOR) as well as low expressions of PSA, phospho-S6 ribosomal protein (pS6) and PanCK were associated with BCR. On multivariable analysis, GS, pT, and immunohistochemical expressions of PanCK and p-mTOR remained independent prognostic factors for BCR.
CONCLUSIONS
These results suggest GS, pT, and immunohistochemical expressions of PanCK and p-mTOR as independent prognostic factors for BCR in DAC. Since DAC showed diverse expression of prostate cancer-related proteins, this should be recognized in interpreting the immunoprofile of DAC. The diverse expression of mTOR-related proteins implicates their potential utility as predictive markers for mTOR targeted therapy.

Keyword

Prostatic neoplasms; Carcinoma, ductal; Immunohistochemistry; Prognosis

MeSH Terms

Adenocarcinoma*
Carcinoma, Ductal
Follow-Up Studies
Immunohistochemistry
Neoplasm Grading
Prognosis
Prostate*
Prostate-Specific Antigen
Prostatic Neoplasms
Recurrence
Ribosomal Proteins
Sirolimus
Tumor Burden
Prostate-Specific Antigen
Ribosomal Proteins
Sirolimus

Figure

• 

  Fig. 1. Representative cases with strong intensity of each immunohistochemical staining: pan-cytokeratin (A), prostate-specific antigen (B), androgen receptor (C), ETS-related gene (D), p53 (E), enhancer of zeste homolog 2 (F), phosphatase and tensin homolog (G), phosphomammalian target of rapamycin (H), phospho-S6 ribosomal protein (I), and 14-3-3 sigma (J).

• 

  Fig. 2. (A) Box and whisker plot with overlying scatterplot to visualize distributions of the immunoreactive tumor cell proportions against the prostate cancer–related proteins in ductal adenocarcinoma. About 15% of the cases (9 of 61) exhibited a completely negative reaction for pan-cytokeratin (PanCK). (B) The same plot to demonstrate the positive tumor cell proportions against the proteins related to the mammalian target of rapamycin (mTOR) pathway. PSA, prostate-specific antigen; AR, androgen receptor; ERG, ETS-related gene; EZH2, enhancer of zeste homolog 2; PTEN, phosphatase and tensin homolog; p-mTOR, phospho-mammalian target of rapamycin; pS6, phospho-S6 ribosomal protein.

• 

  Fig. 3. Pan-cytokeratin (PanCK) immunohistochemistry on whole section slides. All nine cases of PanCK-negative on tissue microarray (TMA) were immunostained for PanCK on whole section, and then their scan view images were presented. PanCK was still negative in eight cases (A–H) on the whole sections except one case (I), which showed focal (15%) immunopositivity (ductal adenocarcinoma, blue line; acinar adenocarcinoma component, red line; normal prostate glands, black line; round empty space, TMA site).

• 

  Fig. 4. Kaplan-Meier survival curves of four independent prognostic factors on biochemical recurrence. The Kaplan-Meier survival curves are well-established according to Gleason score (GS) and pT stage (A, B). The prognosis is worse with less than 50% expression in pan-cytokeratin (PanCK) staining (C), and with more than 40% expression in phospho-mammalian target of rapamycin (p-mTOR) staining (D).

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