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Table 4 Expression of stem/cancer stem cell (OCT4, SSEA-4, CD44, LGR5, ALDH) and proliferation (KI67) markers after dual labeling of ovarian tissue and tumors

From: Characterization of stem cell and cancer stem cell populations in ovary and ovarian tumors

Markers/Genes

HG-OSE

HG-Cortex

OCT4+/KI67+

O+(n)/K+(c), O+(n)/K+(n)

O+(n)/K+(n), O+/K−

SSEA-4+/KI67+

S4+/K+(n)

S4−/K+(n), S4+/K−, S4+/K+(c)

Inference: Stem cell and proliferation marker both are being co-expressed in OSE cells and cortex region (O+/K+ and S4+/K+). Few non-proliferating (KI67−) OCT4+ cells were also observed in the cortex region. KI67 was expressed in active phases of cell cycle [G (1), S, G (2)], and mitosis) among the non-stem cancer/tumor cells as well as in CSCs. Majority of the cells expressing OCT4 in cortex region were also in proliferation state [O+(n)/K+(n), O+(n)/K+(c)].

Similarly OSE and cortical cells also expressed surface/cytoplasmic (SSEA-4) and proliferation (KI67) markers [S4+/K+(n), S4+/K+(c)]. Some cells in cortex were active in cell cycle but failed to express stem cell characteristics signifying probable non-stem cancer cells within the tumor. Some KI67− cells with stem cell properties were observed [S4+/K−] thus indicating their quiescent/non-proliferating state of cell cycle/dormancy [S4+(c) /K+(c), S4+(c) /K+(n)].

KI67(c) cells are typically observed in cancer tissue and by virtue of expression of OCT4+ [O+(n)/K+(n), O+(n)/K+(c)] and SSEA-4+ [S4+/K+(c)] stem cell properties signify a proliferating population of stem cells with probable tumorigenic potential.

CD44+/KI67+

C44+/K+(c)/(m)

C44+/K+(n), C44+/K+(c), C44−/K+(m)

LGR5+/KI67+

L5+/K+(c), (m) (OSE cells and clusters)

L5+/K+(m)

ALDH+/KI67+

A+/K+(c) spindle shaped cells)

A+/K−, A+/K+(c)/(m)

Inference: Co-expression of cancer stem cell (CD44, LGR5, ALDH) and proliferation (KI67) markers in the OSE layer and cortex regions both (C44+/K+, L5+/K+, ALDH+/K+) denote prevalence of very potent populations/sub-populations of actively proliferating CSCs. LGR5 expression alone also indicates proliferating stem cells. Therefore L5+/K− cell types were not reported.

However differential expression of dual markers in both ovarian regions signifies various stages of differentiation and proliferation status of CSCs. KI67(c), (m) expression along with diverse cancer stem cell characteristics [C44+/K+(c), C44−/K+(m), L5+/K+(m), A+/K+(c)] reflects existence of dynamic populations of proliferating CSCs indeed.

  1. +: positive expression; −: negative/nil expression
  2. O: OCT4, S4: SSEA4, K: KI67, C44: CD44, L5: LGR5, A: ALDH1/2;
  3. (c): cytoplasmic localization; (m): membrane localization; (n): nuclear localization